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Sample records for grb cleavage sites

  1. Dataset of cocoa aspartic protease cleavage sites

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    Katharina Janek

    2016-09-01

    Full Text Available The data provide information in support of the research article, “The cleavage specificity of the aspartic protease of cocoa beans involved in the generation of the cocoa-specific aroma precursors” (Janek et al., 2016 [1]. Three different protein substrates were partially digested with the aspartic protease isolated from cocoa beans and commercial pepsin, respectively. The obtained peptide fragments were analyzed by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS/MS and identified using the MASCOT server. The N- and C-terminal ends of the peptide fragments were used to identify the corresponding in-vitro cleavage sites by comparison with the amino acid sequences of the substrate proteins. The same procedure was applied to identify the cleavage sites used by the cocoa aspartic protease during cocoa fermentation starting from the published amino acid sequences of oligopeptides isolated from fermented cocoa beans. Keywords: Aspartic protease, Cleavage sites, Cocoa, In-vitro proteolysis, Mass spectrometry, Peptides

  2. Pripper: prediction of caspase cleavage sites from whole proteomes

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    Salmi Jussi

    2010-06-01

    Full Text Available Abstract Background Caspases are a family of proteases that have central functions in programmed cell death (apoptosis and inflammation. Caspases mediate their effects through aspartate-specific cleavage of their target proteins, and at present almost 400 caspase substrates are known. There are several methods developed to predict caspase cleavage sites from individual proteins, but currently none of them can be used to predict caspase cleavage sites from multiple proteins or entire proteomes, or to use several classifiers in combination. The possibility to create a database from predicted caspase cleavage products for the whole genome could significantly aid in identifying novel caspase targets from tandem mass spectrometry based proteomic experiments. Results Three different pattern recognition classifiers were developed for predicting caspase cleavage sites from protein sequences. Evaluation of the classifiers with quality measures indicated that all of the three classifiers performed well in predicting caspase cleavage sites, and when combining different classifiers the accuracy increased further. A new tool, Pripper, was developed to utilize the classifiers and predict the caspase cut sites from an arbitrary number of input sequences. A database was constructed with the developed tool, and it was used to identify caspase target proteins from tandem mass spectrometry data from two different proteomic experiments. Both known caspase cleavage products as well as novel cleavage products were identified using the database demonstrating the usefulness of the tool. Pripper is not restricted to predicting only caspase cut sites, but it gives the possibility to scan protein sequences for any given motif(s and predict cut sites once a suitable cut site prediction model for any other protease has been developed. Pripper is freely available and can be downloaded from http://users.utu.fi/mijopi/Pripper. Conclusions We have developed Pripper, a tool for

  3. Variable context Markov chains for HIV protease cleavage site prediction.

    Science.gov (United States)

    Oğul, Hasan

    2009-06-01

    Deciphering the knowledge of HIV protease specificity and developing computational tools for detecting its cleavage sites in protein polypeptide chain are very desirable for designing efficient and specific chemical inhibitors to prevent acquired immunodeficiency syndrome. In this study, we developed a generative model based on a generalization of variable order Markov chains (VOMC) for peptide sequences and adapted the model for prediction of their cleavability by certain proteases. The new method, called variable context Markov chains (VCMC), attempts to identify the context equivalence based on the evolutionary similarities between individual amino acids. It was applied for HIV-1 protease cleavage site prediction problem and shown to outperform existing methods in terms of prediction accuracy on a common dataset. In general, the method is a promising tool for prediction of cleavage sites of all proteases and encouraged to be used for any kind of peptide classification problem as well.

  4. Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2.

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    Ambarish Nag

    Full Text Available The linker for activation of T cells (LAT, the linker for activation of B cells (LAB, and the linker for activation of X cells (LAX form a family of transmembrane adaptor proteins widely expressed in lymphocytes. These scaffolding proteins have multiple binding motifs that, when phosphorylated, bind the SH2 domain of the cytosolic adaptor Grb2. Thus, the valence of LAT, LAB and LAX for Grb2 is variable, depending on the strength of receptor activation that initiates phosphorylation. During signaling, the LAT population will exhibit a time-varying distribution of Grb2 valences from zero to three. In the cytosol, Grb2 forms 1:1 and 2:1 complexes with the guanine nucleotide exchange factor SOS1. The 2:1 complex can bridge two LAT molecules when each Grb2, through their SH2 domains, binds to a phosphorylated site on a separate LAT. In T cells and mast cells, after receptor engagement, receptor phosphoyrlation is rapidly followed by LAT phosphorylation and aggregation. In mast cells, aggregates containing more than one hundred LAT molecules have been detected. Previously we considered a homogeneous population of trivalent LAT molecules and showed that for a range of Grb2, SOS1 and LAT concentrations, an equilibrium theory for LAT aggregation predicts the formation of a gel-like phase comprising a very large aggregate (superaggregate. We now extend this theory to investigate the effects of a distribution of Grb2 valence in the LAT population on the formation of LAT aggregates and superaggregate and use stochastic simulations to calculate the fraction of the total LAT population in the superaggregate.

  5. Active site mutations change the cleavage specificity of neprilysin.

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    Travis Sexton

    Full Text Available Neprilysin (NEP, a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe(563 and Ser(546. Among the mutants studied in detail we observed changes in their activity towards leucine(5-enkephalin, insulin B chain, and amyloid β(1-40. For example, NEP(F563I displayed an increase in preference towards cleaving leucine(5-enkephalin relative to insulin B chain, while mutant NEP(S546E was less discriminating than neprilysin. Mutants NEP(F563L and NEP(S546E exhibit different cleavage site preferences than neprilysin with insulin B chain and amyloid ß(1-40 as substrates. These data indicate that it is possible to alter the cleavage site specificity of neprilysin opening the way for the development of substrate specific or substrate exclusive forms of the enzyme with enhanced therapeutic potential.

  6. Cleavage sites within the poliovirus capsid protein precursors

    International Nuclear Information System (INIS)

    Larsen, G.R.; Anderson, C.W.; Dorner, A.J.; Semler, B.L.; Wimmer, E.

    1982-01-01

    Partial amino-terminal sequence analysis was performed on radiolabeled poliovirus capsid proteins VP1, VP2, and VP3. A computer-assisted comparison of the amino acid sequences obtained with that predicted by the nucleotide sequence of the poliovirus genome allows assignment of the amino terminus of each capsid protein to a unique position within the virus polyprotein. Sequence analysis of trypsin-digested VP4, which has a blocked amino terminus, demonstrates that VP4 is encoded at or very near to the amino terminus of the polyprotein. The gene order of the capsid proteins is VP4-VP2-VP3-VP1. Cleavage of VP0 to VP4 and VP2 is shown to occur between asparagine and serine, whereas the cleavages that separate VP2/VP3 and VP3/VP1 occur between glutamine and glycine residues. This finding supports the hypothesis that the cleavage of VP0, which occurs during virion morphogenesis, is distinct from the cleavages that separate functional regions of the polyprotein

  7. Coronavirus 3CLpro proteinase cleavage sites: Possible relevance to SARS virus pathology

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    Blom Nikolaj

    2004-06-01

    Full Text Available Abstract Background Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS, efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. Results We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR, transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. Conclusions Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website: http://www.cbs.dtu.dk/services/NetCorona/.

  8. Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases.

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    Schlaepfer, D D; Hunter, T

    1996-10-01

    Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase (PTK) that associates with integrin receptors and participates in extracellular matrix-mediated signal transduction events. We showed previously that the c-Src nonreceptor PTK and the Grb2 SH2/SH3 adaptor protein bound directly to FAK after fibronectin stimulation (D. D. Schlaepfer, S.K. Hanks, T. Hunter, and P. van der Geer, Nature [London] 372:786-791, 1994). Here, we present evidence that c-Src association with FAK is required for Grb2 binding to FAK. Using a tryptic phosphopeptide mapping approach, the in vivo phosphorylation of the Grb2 binding site on FAK (Tyr-925) was detected after fibronectin stimulation of NIH 3T3 cells and was constitutively phosphorylated in v-Src-transformed NIH 3T3 cells. In vitro, c-Src phosphorylated FAK Tyr-925 in a glutathione S-transferase-FAK C-terminal domain fusion protein, whereas FAK did not. Using epitope-tagged FAK constructs, transiently expressed in human 293 cells, we determined the effect of site-directed mutations on c-Src and Grb2 binding to FAK. Mutation of FAK Tyr-925 disrupted Grb2 binding, whereas mutation of the c-Src binding site on FAK (Tyr-397) disrupted both c-Src and Grb2 binding to FAK in vivo. These results support a model whereby Src-family PTKs are recruited to FAK and focal adhesions following integrin-induced autophosphorylation and exposure of FAK Tyr-397. Src-family binding and phosphorylation of FAK at Tyr-925 creates a Grb2 SH2-domain binding site and provides a link to the activation of the Ras signal transduction pathway. In Src-transformed cells, this pathway may be constitutively activated as a result of FAK Tyr-925 phosphorylation in the absence of integrin stimulation.

  9. PROSPER: an integrated feature-based tool for predicting protease substrate cleavage sites.

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    Jiangning Song

    Full Text Available The ability to catalytically cleave protein substrates after synthesis is fundamental for all forms of life. Accordingly, site-specific proteolysis is one of the most important post-translational modifications. The key to understanding the physiological role of a protease is to identify its natural substrate(s. Knowledge of the substrate specificity of a protease can dramatically improve our ability to predict its target protein substrates, but this information must be utilized in an effective manner in order to efficiently identify protein substrates by in silico approaches. To address this problem, we present PROSPER, an integrated feature-based server for in silico identification of protease substrates and their cleavage sites for twenty-four different proteases. PROSPER utilizes established specificity information for these proteases (derived from the MEROPS database with a machine learning approach to predict protease cleavage sites by using different, but complementary sequence and structure characteristics. Features used by PROSPER include local amino acid sequence profile, predicted secondary structure, solvent accessibility and predicted native disorder. Thus, for proteases with known amino acid specificity, PROSPER provides a convenient, pre-prepared tool for use in identifying protein substrates for the enzymes. Systematic prediction analysis for the twenty-four proteases thus far included in the database revealed that the features we have included in the tool strongly improve performance in terms of cleavage site prediction, as evidenced by their contribution to performance improvement in terms of identifying known cleavage sites in substrates for these enzymes. In comparison with two state-of-the-art prediction tools, PoPS and SitePrediction, PROSPER achieves greater accuracy and coverage. To our knowledge, PROSPER is the first comprehensive server capable of predicting cleavage sites of multiple proteases within a single substrate

  10. Degradation of tropoelastin by matrix metalloproteinases--cleavage site specificities and release of matrikines

    DEFF Research Database (Denmark)

    Heinz, Andrea; Jung, Michael C; Duca, Laurent

    2010-01-01

    To provide a basis for the development of approaches to treat elastin-degrading diseases, the aim of this study was to investigate the degradation of the natural substrate tropoelastin by the elastinolytic matrix metalloproteinases MMP-7, MMP-9, and MMP-12 and to compare the cleavage site...

  11. Rendering one autolysis site in Bacillus subtilis neutral protease resistant to cleavage reveals a new fission

    NARCIS (Netherlands)

    Van den Burg, B; Eijsink, VGH; Vriend, G; Veltman, OR; Venema, G

    Autolytic degradation of the thermolysin-like proteinase of Bacillus subtilis (TLP-sub) is responsible for the irreversible inactivation of the enzyme at elevated temperatures. Previously we have reported five cleavage sites in Tip-sub [Van den Burg et al, (1990) Biochem. J. 272, 93-97]. In an

  12. Characterization of a Non-Canonical Signal Peptidase Cleavage Site in a Replication Protein from Tomato Ringspot Virus.

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    Ting Wei

    Full Text Available The NTB-VPg polyprotein from tomato ringspot virus is an integral membrane replication protein associated with endoplasmic reticulum membranes. A signal peptidase (SPase cleavage was previously detected in the C-terminal region of NTB-VPg downstream of a 14 amino acid (aa-long hydrophobic region (termed TM2. However, the exact location of the cleavage site was not determined. Using in vitro translation assays, we show that the SPase cleavage site is conserved in the NTB-VPg protein from various ToRSV isolates, although the rate of cleavage varies from one isolate to another. Systematic site-directed mutagenesis of the NTB-VPg SPase cleavage sites of two ToRSV isolates allowed the identification of sequences that affect cleavage efficiency. We also present evidence that SPase cleavage in the ToRSV-Rasp2 isolate occurs within a GAAGG sequence likely after the AAG (GAAG/G. Mutation of a downstream MAAV sequence to AAAV resulted in SPase cleavage at both the natural GAAG/G and the mutated AAA/V sequences. Given that there is a distance of seven aa between the two cleavage sites, this indicates that there is flexibility in the positioning of the cleavage sites relative to the inner surface of the membrane and the SPase active site. SPase cleavage sites are typically located 3-7 aa downstream of the hydrophobic region. However, the NTB-VPg GAAG/G cleavage site is located 17 aa downstream of the TM2 hydrophobic region, highlighting unusual features of the NTB-VPg SPase cleavage site. A putative 11 aa-long amphipathic helix was identified immediately downstream of the TM2 region and five aa upstream of the GAAG/G cleavage site. Based on these results, we present an updated topology model in which the hydrophobic and amphipathic domains form a long tilted helix or a bent helix in the membrane lipid bilayer, with the downstream cleavage site(s oriented parallel to the membrane inner surface.

  13. Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3.

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    Shoba Subramanian

    Full Text Available The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P(1 - P(4 amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P(2 position. Second, with overlapping peptides spanning alpha and beta globin and proteolysis-dependent (18O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P(2 Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents.

  14. Signal peptide discrimination and cleavage site identification using SVM and NN.

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    Kazemian, H B; Yusuf, S A; White, K

    2014-02-01

    About 15% of all proteins in a genome contain a signal peptide (SP) sequence, at the N-terminus, that targets the protein to intracellular secretory pathways. Once the protein is targeted correctly in the cell, the SP is cleaved, releasing the mature protein. Accurate prediction of the presence of these short amino-acid SP chains is crucial for modelling the topology of membrane proteins, since SP sequences can be confused with transmembrane domains due to similar composition of hydrophobic amino acids. This paper presents a cascaded Support Vector Machine (SVM)-Neural Network (NN) classification methodology for SP discrimination and cleavage site identification. The proposed method utilises a dual phase classification approach using SVM as a primary classifier to discriminate SP sequences from Non-SP. The methodology further employs NNs to predict the most suitable cleavage site candidates. In phase one, a SVM classification utilises hydrophobic propensities as a primary feature vector extraction using symmetric sliding window amino-acid sequence analysis for discrimination of SP and Non-SP. In phase two, a NN classification uses asymmetric sliding window sequence analysis for prediction of cleavage site identification. The proposed SVM-NN method was tested using Uni-Prot non-redundant datasets of eukaryotic and prokaryotic proteins with SP and Non-SP N-termini. Computer simulation results demonstrate an overall accuracy of 0.90 for SP and Non-SP discrimination based on Matthews Correlation Coefficient (MCC) tests using SVM. For SP cleavage site prediction, the overall accuracy is 91.5% based on cross-validation tests using the novel SVM-NN model. © 2013 Published by Elsevier Ltd.

  15. Conservation of a proteinase cleavage site between an insect retrovirus (gypsy) Env protein and a baculovirus envelope fusion protein

    International Nuclear Information System (INIS)

    Pearson, Margot N.; Rohrmann, George F.

    2004-01-01

    The predicted Env protein of insect retroviruses (errantiviruses) is related to the envelope fusion protein of a major division of the Baculoviridae. The highest degree of homology is found in a region that contains a furin cleavage site in the baculovirus proteins and an adjacent sequence that has the properties of a fusion peptide. In this investigation, the homologous region in the Env protein of the gypsy retrovirus of Drosophila melanogaster (DmegypV) was investigated. Alteration of the predicted DmegypV Env proteinase cleavage site from RIAR to AIAR significantly reduced cleavage of Env in both Spodoptera frugiperda (Sf-9) and D. melanogaster (S2) cell lines. When the predicted DmegypV Env cleavage site RIAR was substituted for the cleavage sequence RRKR in the Lymantria dispar nucleopolyhedrovirus fusion protein (LD130) sequence, cleavage of the hybrid LD130 molecules still occurred, although at a reduced level. The conserved 21-amino acid sequence just downstream of the cleavage site, which is thought to be the fusion peptide in LD130, was also characterized. When this sequence from DmegypV Env was substituted for the homologous sequence in LD130, cleavage still occurred, but no fusion was observed in either cell type. In addition, although a DmegypV-Env-green fluorescent protein construct localized to cell membranes, no cell fusion was observed

  16. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

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    Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique

    2016-07-15

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.

  17. Identification of succinimide sites in proteins by N-terminal sequence analysis after alkaline hydroxylamine cleavage.

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    Kwong, M. Y.; Harris, R. J.

    1994-01-01

    Under favorable conditions, Asp or Asn residues can undergo rearrangement to a succinimide (cyclic imide), which may also serve as an intermediate for deamidation and/or isoaspartate formation. Direct identification of such succinimides by peptide mapping is hampered by their lability at neutral and alkaline pH. We determined that incubation in 2 M hydroxylamine, 0.2 M Tris buffer, pH 9, for 2 h at 45 degrees C will specifically cleave on the C-terminal side of succinimides without cleavage at Asn-Gly bonds; yields are typically approximately 50%. N-terminal sequence analysis can then be used to identify an internal sequence generated by cleavage of the succinimide, hence identifying the succinimide site. PMID:8142891

  18. Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus

    Science.gov (United States)

    Licitra, Beth N.; Millet, Jean K.; Regan, Andrew D.; Hamilton, Brian S.; Rinaldi, Vera D.; Duhamel, Gerald E.

    2013-01-01

    Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses. PMID:23763835

  19. Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site and Involved Proteases.

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    Nicole Hofmann

    Full Text Available ABCA3 is a lipid transporter in the limiting membrane of lamellar bodies in alveolar type II cells. Mutations in the ABCA3 gene cause respiratory distress syndrome in new-borns and childhood interstitial lung disease. ABCA3 is N-terminally cleaved by an as yet unknown protease, a process believed to regulate ABCA3 activity.The exact site where ABCA3 is cleaved was localized using mass spectrometry (MS. Proteases involved in ABCA3 processing were identified using small molecule inhibitors and siRNA mediated gene knockdown. Results were verified by in vitro digestion of a synthetic peptide substrate mimicking ABCA3's cleavage region, followed by MS analysis.We found that cleavage of ABCA3 occurs after Lys174 which is located in the proteins' first luminal loop. Inhibition of cathepsin L and, to a lesser extent, cathepsin B resulted in attenuation of ABCA3 cleavage. Both enzymes showed activity against the ABCA3 peptide in vitro with cathepsin L being more active.We show here that, like some other proteins of the lysosomal membrane, ABCA3 is a substrate of cathepsin L. Therefore, cathepsin L may represent a potential target to therapeutically influence ABCA3 activity in ABCA3-associated lung disease.

  20. Snake venom serine proteinases specificity mapping by proteomic identification of cleavage sites.

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    Zelanis, André; Huesgen, Pitter F; Oliveira, Ana Karina; Tashima, Alexandre K; Serrano, Solange M T; Overall, Christopher M

    2015-01-15

    Many snake venom toxins are serine proteases but their specific in vivo targets are mostly unknown. Various act on components of the coagulation cascade, and fibrinolytic and kallikrein-kinin systems to trigger various pathological effects observed in the envenomation. Despite showing high similarity in terms of primary structure snake venom serine proteinases (SVSPs) show exquisite specificity towards macromolecular substrates. Therefore, the characterization of their peptide bond specificity is important for understanding the active site preference associated with effective proteolysis as well as for the design of peptide substrates and inhibitors. Bothrops jararaca contains various SVSPs among which Bothrops protease A is a specific fibrinogenolytic agent and PA-BJ is a platelet-activating enzyme. In this study we used proteome derived peptide libraries in the Proteomic Identification of protease Cleavage Sites (PICS) approach to explore the peptide bond specificity of Bothrops protease A and PA-BJ in order to determine their individual peptide cleavage sequences. A total of 371 cleavage sites (208 for Bothrops protease A and 163 for PA-BJ) were detected and both proteinases displayed a clear preference for arginine at the P1 position. Moreover, the analysis of the specificity profiles of Bothrops protease A and PA-BJ revealed subtle differences in the preferences along P6-P6', despite a common yet unusual preference for Pro at P2. Taken together, these results map the subsite specificity of both SVSPs and shed light in the functional differences between these proteinases. Proteolysis is key to various pathological effects observed upon envenomation by viperid snakes. The use of the Proteomic Identification of protease Cleavage Sites (PICS) approach for the easy mapping of proteinase subsite preferences at both the prime- and non-prime sides concurrently gives rise to a fresh understanding of the interaction of the snake venom serine proteinases with peptide and

  1. GRB 051008

    DEFF Research Database (Denmark)

    Volnova, A. A.; Pozanenko, A. S.; Gorosabel, J.

    2014-01-01

    due to the presence of a clear, strong Lyman-break feature. The host galaxy is a small starburst galaxy with moderate intrinsic extinction (AV = 0.3) and has a star formation rate of ∼60 M⊙ yr−1 typical for LBGs. It is one of the few cases where a GRB host has been found to be a classical LBG. Using...

  2. Base substitutions at scissile bond sites are sufficient to alter RNA-binding and cleavage activity of RNase III.

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    Kim, Kyungsub; Sim, Se-Hoon; Jeon, Che Ok; Lee, Younghoon; Lee, Kangseok

    2011-02-01

    RNase III, a double-stranded RNA-specific endoribonuclease, degrades bdm mRNA via cleavage at specific sites. To better understand the mechanism of cleavage site selection by RNase III, we performed a genetic screen for sequences containing mutations at the bdm RNA cleavage sites that resulted in altered mRNA stability using a transcriptional bdm'-'cat fusion construct. While most of the isolated mutants showed the increased bdm'-'cat mRNA stability that resulted from the inability of RNase III to cleave the mutated sequences, one mutant sequence (wt-L) displayed in vivo RNA stability similar to that of the wild-type sequence. In vivo and in vitro analyses of the wt-L RNA substrate showed that it was cut only once on the RNA strand to the 5'-terminus by RNase III, while the binding constant of RNase III to this mutant substrate was moderately increased. A base substitution at the uncleaved RNase III cleavage site in wt-L mutant RNA found in another mutant lowered the RNA-binding affinity by 11-fold and abolished the hydrolysis of scissile bonds by RNase III. Our results show that base substitutions at sites forming the scissile bonds are sufficient to alter RNA cleavage as well as the binding activity of RNase III. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  3. Effects of mutations in the VP2/VP4 cleavage site of Swine vesicular disease virus on RNA encapsidation and viral infectivity

    NARCIS (Netherlands)

    Rebel, J.M.J.; Leendertse, C.H.; Dekker, A.; Moormann, R.J.M.

    2003-01-01

    We studied VP0 cleavage of Swine vesicular disease virus (SVDV), a member of the Picornaviridae using a full-length cDNA copy of the Dutch SVDV isolate. The influences of mutations, introduced at the cleavage site of SVDV, on VP0 cleavage, RNA encapsidation and viral infection were studied. Double

  4. ChloroP, a neural network-based method for predicting chloroplast transitpeptides and their cleavage sites

    DEFF Research Database (Denmark)

    Emanuelsson, O.; Nielsen, Henrik; von Heijne, Gunnar

    1999-01-01

    the cleavage sites given in SWISS-PROT. An analysis of 715 Arabidopsis thaliana sequences from SWISS-PROT suggests that the ChloroP method should be useful for the identification of putative transit peptides in genome-wide sequence data. The ChloroP predictor is available as a web-server at http......We present a neural network based method (ChloroP) for identifying chloroplast transit peptides and their cleavage sites. Using cross-validation, 88% of the sequences in our homology reduced training set were correctly classified as transit peptides or nontransit peptides. This performance level...

  5. Isolation of recombinant phage antibodies targeting the hemagglutinin cleavage site of highly pathogenic avian influenza virus.

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    Jinhua Dong

    Full Text Available Highly pathogenic avian influenza (HPAI H5N1 viruses, which have emerged in poultry and other wildlife worldwide, contain a characteristic multi-basic cleavage site (CS in the hemagglutinin protein (HA. Because this arginine-rich CS is unique among influenza virus subtypes, antibodies against this site have the potential to specifically diagnose pathogenic H5N1. By immunizing mice with the CS peptide and screening a phage display library, we isolated four antibody Fab fragment clones that specifically bind the antigen peptide and several HPAI H5N1 HA proteins in different clades. The soluble Fab fragments expressed in Escherichia coli bound the CS peptide and the H5N1 HA protein with nanomolar affinity. In an immunofluorescence assay, these Fab fragments stained cells infected with HPAI H5N1 but not those infected with a less virulent strain. Lastly, all the Fab clones could detect the CS peptide and H5N1 HA protein by open sandwich ELISA. Thus, these recombinant Fab fragments will be useful novel reagents for the rapid and specific detection of HPAI H5N1 virus.

  6. Model for how type I restriction enzymes select cleavage sites in DNA

    International Nuclear Information System (INIS)

    Studier, F.W.; Bandyopadhyay, P.K.

    1988-01-01

    Under appropriate conditions, digestion of phage T7 DNA by the type I restriction enzyme EcoK produces an orderly progression of discrete DNA fragments. All details of the fragmentation pattern can be explained on the basis of the known properties of type I enzymes, together with two further assumptions: (i) in the ATP-stimulated translocation reaction, the enzyme bound at the recognition sequence translocates DNA toward itself from both directions simultaneously; and (ii) when translocation causes neighboring enzymes to meet, they cut the DNA between them. The kinetics of digestion at 37 degree C indicates that the rate of translocation of DNA from each side of a bound enzyme is about 200 base pairs per second, and the cuts are completed within 15-25 sec of the time neighboring enzymes meet. The resulting DNA fragments each contain a single recognition site with an enzyme (or subunit) remaining bound to it. At high enzyme concentrations, such fragments can bu further degraded, apparently by cooperation between the specifically bound and excess enzymes. This model is consistent with a substantial body of previous work on the nuclease activity of EcoB and EcoK, and it explains in a simple way how cleavage sites are selected

  7. A neural network method for identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engelbrecht, Jacob; Brunak, Søren

    1997-01-01

    We have developed a new method for the identication of signal peptides and their cleavage sites based on neural networks trained on separate sets of prokaryotic and eukaryotic sequences. The method performs signicantly better than previous prediction schemes, and can easily be applied to genome...

  8. Acquisition of a novel eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site confers intracellular cleavage of an H7N7 influenza virus hemagglutinin

    International Nuclear Information System (INIS)

    Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik; Whittaker, Gary R.

    2012-01-01

    A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.

  9. Acquisition of a novel eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site confers intracellular cleavage of an H7N7 influenza virus hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States); Whittaker, Gary R., E-mail: grw7@cornell.edu [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States)

    2012-12-05

    A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.

  10. A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties

    Science.gov (United States)

    Millet, Jean Kaoru; Goldstein, Monty E; Labitt, Rachael N; Hsu, Hung-Lun; Daniel, Susan; Whittaker, Gary R

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution. PMID:27999426

  11. Coronavirus 3CL(pro) proteinase cleavage sites: Possible relevance to SARS virus pathology

    DEFF Research Database (Denmark)

    Kiemer, Lars; Lund, Ole; Brunak, Søren

    2004-01-01

    the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection...

  12. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engelbrecht, Jacob; Brunak, Søren

    1997-01-01

    We have developed a new method for the identification of signal peptides and their cleavage based on neural networks trained on separate sets of prokaryotic and eukaryotic sequence. The method performs significantly better than previous prediction schemes and can easily be applied on genome...

  13. Sequence motif upstream of the Hendra virus fusion protein cleavage site is not sufficient to promote efficient proteolytic processing

    International Nuclear Information System (INIS)

    Craft, Willie Warren; Dutch, Rebecca Ellis

    2005-01-01

    The Hendra virus fusion (HeV F) protein is synthesized as a precursor, F 0 , and proteolytically cleaved into the mature F 1 and F 2 heterodimer, following an HDLVDGVK 109 motif. This cleavage event is required for fusogenic activity. To determine the amino acid requirements for processing of the HeV F protein, we constructed multiple mutants. Individual and simultaneous alanine substitutions of the eight residues immediately upstream of the cleavage site did not eliminate processing. A chimeric SV5 F protein in which the furin site was substituted for the VDGVK 109 motif of the HeV F protein was not processed but was expressed on the cell surface. Another chimeric SV5 F protein containing the HDLVDGVK 109 motif of the HeV F protein underwent partial cleavage. These data indicate that the upstream region can play a role in protease recognition, but is neither absolutely required nor sufficient for efficient processing of the HeV F protein

  14. Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

    Science.gov (United States)

    Luczo, Jasmina M.; Stambas, John; Durr, Peter A.; Michalski, Wojtek P.

    2015-01-01

    Summary The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio‐economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host‐pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:26467906

  15. Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA

    Science.gov (United States)

    Schmidt, Thomas P.; Perna, Anna M.; Fugmann, Tim; Böhm, Manja; Jan Hiss; Haller, Sarah; Götz, Camilla; Tegtmeyer, Nicole; Hoy, Benjamin; Rau, Tilman T.; Neri, Dario; Backert, Steffen; Schneider, Gisbert; Wessler, Silja

    2016-03-01

    The cell adhesion protein and tumour suppressor E-cadherin exhibits important functions in the prevention of gastric cancer. As a class-I carcinogen, Helicobacter pylori (H. pylori) has developed a unique strategy to interfere with E-cadherin functions. In previous studies, we have demonstrated that H. pylori secretes the protease high temperature requirement A (HtrA) which cleaves off the E-cadherin ectodomain (NTF) on epithelial cells. This opens cell-to-cell junctions, allowing bacterial transmigration across the polarised epithelium. Here, we investigated the molecular mechanism of the HtrA-E-cadherin interaction and identified E-cadherin cleavage sites for HtrA. Mass-spectrometry-based proteomics and Edman degradation revealed three signature motifs containing the [VITA]-[VITA]-x-x-D-[DN] sequence pattern, which were preferentially cleaved by HtrA. Based on these sites, we developed a substrate-derived peptide inhibitor that selectively bound and inhibited HtrA, thereby blocking transmigration of H. pylori. The discovery of HtrA-targeted signature sites might further explain why we detected a stable 90 kDa NTF fragment during H. pylori infection, but also additional E-cadherin fragments ranging from 105 kDa to 48 kDa in in vitro cleavage experiments. In conclusion, HtrA targets E-cadherin signature sites that are accessible in in vitro reactions, but might be partially masked on epithelial cells through functional homophilic E-cadherin interactions.

  16. Positioning the 5'-flap junction in the active site controls the rate of flap endonuclease-1-catalyzed DNA cleavage

    KAUST Repository

    Song, Bo

    2018-02-09

    Flap endonucleases catalyze cleavage of single-stranded DNA flaps formed during replication, repair and recombination, and are therefore essential for genome processing and stability. Recent crystal structures of DNA-bound human flap endonuclease (hFEN1) offer new insights into how conformational changes in the DNA and hFEN1 may facilitate the reaction mechanism. For example, previous biochemical studies of DNA conformation performed under non-catalytic conditions with Ca2+ have suggested that base unpairing at the 5\\'-flap:template junction is an important step in the reaction, but the new structural data suggest otherwise. To clarify the role of DNA changes in the kinetic mechanism, we measured a series of transient steps - from substrate binding to product release - during the hFEN1-catalyzed reaction in the presence of Mg2+. We found that while hFEN1 binds and bends DNA at a fast, diffusion-limited rate, much slower Mg2+-dependent conformational changes in DNA around the active site are subsequently necessary and rate-limiting for 5\\'-flap cleavage. These changes are reported overall by fluorescence of 2-aminopurine at the 5\\'-flap:template junction, indicating that local DNA distortion (e.g., disruption of base stacking observed in structures), associated with positioning the 5\\'-flap scissile phosphodiester bond in the hFEN1 active site, controls catalysis. hFEN1 residues with distinct roles in the catalytic mechanism, including those binding metal ions (Asp-34, Asp-181), steering the 5\\'-flap through the active site and binding the scissile phosphate (Lys-93, Arg-100), and stacking against the base 5\\' to the scissile phosphate (Tyr-40), all contribute to these rate-limiting conformational changes, ensuring efficient and specific cleavage of 5\\'-flaps.

  17. Positioning the 5'-flap junction in the active site controls the rate of flap endonuclease-1-catalyzed DNA cleavage

    KAUST Repository

    Song, Bo; Hamdan, Samir; Hingorani, Manju M

    2018-01-01

    Flap endonucleases catalyze cleavage of single-stranded DNA flaps formed during replication, repair and recombination, and are therefore essential for genome processing and stability. Recent crystal structures of DNA-bound human flap endonuclease (hFEN1) offer new insights into how conformational changes in the DNA and hFEN1 may facilitate the reaction mechanism. For example, previous biochemical studies of DNA conformation performed under non-catalytic conditions with Ca2+ have suggested that base unpairing at the 5'-flap:template junction is an important step in the reaction, but the new structural data suggest otherwise. To clarify the role of DNA changes in the kinetic mechanism, we measured a series of transient steps - from substrate binding to product release - during the hFEN1-catalyzed reaction in the presence of Mg2+. We found that while hFEN1 binds and bends DNA at a fast, diffusion-limited rate, much slower Mg2+-dependent conformational changes in DNA around the active site are subsequently necessary and rate-limiting for 5'-flap cleavage. These changes are reported overall by fluorescence of 2-aminopurine at the 5'-flap:template junction, indicating that local DNA distortion (e.g., disruption of base stacking observed in structures), associated with positioning the 5'-flap scissile phosphodiester bond in the hFEN1 active site, controls catalysis. hFEN1 residues with distinct roles in the catalytic mechanism, including those binding metal ions (Asp-34, Asp-181), steering the 5'-flap through the active site and binding the scissile phosphate (Lys-93, Arg-100), and stacking against the base 5' to the scissile phosphate (Tyr-40), all contribute to these rate-limiting conformational changes, ensuring efficient and specific cleavage of 5'-flaps.

  18. The prototype HIV-1 maturation inhibitor, bevirimat, binds to the CA-SP1 cleavage site in immature Gag particles

    Directory of Open Access Journals (Sweden)

    Nguyen Albert T

    2011-12-01

    Full Text Available Abstract Background Bevirimat, the prototype Human Immunodeficiency Virus type 1 (HIV-1 maturation inhibitor, is highly potent in cell culture and efficacious in HIV-1 infected patients. In contrast to inhibitors that target the active site of the viral protease, bevirimat specifically inhibits a single cleavage event, the final processing step for the Gag precursor where p25 (CA-SP1 is cleaved to p24 (CA and SP1. Results In this study, photoaffinity analogs of bevirimat and mass spectrometry were employed to map the binding site of bevirimat to Gag within immature virus-like particles. Bevirimat analogs were found to crosslink to sequences overlapping, or proximal to, the CA-SP1 cleavage site, consistent with previous biochemical data on the effect of bevirimat on Gag processing and with genetic data from resistance mutations, in a region predicted by NMR and mutational studies to have α-helical character. Unexpectedly, a second region of interaction was found within the Major Homology Region (MHR. Extensive prior genetic evidence suggests that the MHR is critical for virus assembly. Conclusions This is the first demonstration of a direct interaction between the maturation inhibitor, bevirimat, and its target, Gag. Information gained from this study sheds light on the mechanisms by which the virus develops resistance to this class of drug and may aid in the design of next-generation maturation inhibitors.

  19. Cleavage sites in the polypeptide precursors of poliovirus protein P2-X

    International Nuclear Information System (INIS)

    Selmer, B.L.; Hanecak, R.; Anderson, C.W.; Wimmer, E.

    1981-01-01

    Partial amino-terminal sequence analysis has been performed on the three major polypeptide products (P2-3b, P2-5b, and P2-X) from the central region (P2) of the poliovirus polyprotein, and this analysis precisely locates the amino termini of these products with respect to the nucleotide sequence of the poliovirus RNA genome. Like most of the products of the replicase region (P3), the amino termini of P2-5b and P2-X are generated by cleavage between glutamine and glycine residues. Thus, P2-5b and P2-X are probably both produced by the action of a singly (virus-encoded.) proteinase. The amino terminus of P2-3b, on the other hand, is produced by a cleavage between the carboxy-terminal tyrosine of VP1 and the glycine encoded by nucleotides 3381-3383. This result may suggest that more than one proteolytic activity is required for the complete processing of the poliovirus polyprotein

  20. SVM-based prediction of propeptide cleavage sites in spider toxins identifies toxin innovation in an Australian tarantula.

    Directory of Open Access Journals (Sweden)

    Emily S W Wong

    Full Text Available Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree and developed an algorithm (SpiderP for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html, a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from

  1. The Conserved ATM Kinase RAG2-S365 Phosphorylation Site Limits Cleavage Events in Individual Cells Independent of Any Repair Defect

    Directory of Open Access Journals (Sweden)

    Susannah L. Hewitt

    2017-10-01

    Full Text Available Many DNA lesions associated with lymphoid malignancies are linked to off-target cleavage by the RAG1/2 recombinase. However, off-target cleavage has mostly been analyzed in the context of DNA repair defects, confounding any mechanistic understanding of cleavage deregulation. We identified a conserved SQ phosphorylation site on RAG2 365 to 366 that is involved in feedback control of RAG cleavage. Mutation of serine 365 to a non-phosphorylatable alanine permits bi-allelic and bi-locus RAG-mediated breaks in the same cell, leading to reciprocal translocations. This phenomenon is analogous to the phenotype we described for ATM kinase inactivation. Here, we establish deregulated cleavage itself as a driver of chromosomal instability without the associated repair defect. Intriguingly, a RAG2-S365E phosphomimetic rescues the deregulated cleavage of ATM inactivation, reducing the incidence of reciprocal translocations. These data support a model in which feedback control of cleavage and maintenance of genome stability involves ATM-mediated phosphorylation of RAG2.

  2. Factor VIII S373L: mutation at P1' site confers thrombin cleavage resistance, causing mild haemophilia A.

    Science.gov (United States)

    Johnson, D J; Pemberton, S; Acquila, M; Mori, P G; Tuddenham, E G; O'Brien, D P

    1994-04-01

    A novel CRM+ mutation, factor VIII position 373 serine to leucine substitution (FVIII 373-Leu) was identified during a survey of Factor VIII (FVIII) mutations. We have purified the variant protein from the patient's plasma in order to allow further characterisation of the molecule. The CRM+ plasma contained 120% Factor VIII antigen (FVIII:Ag) and 6% Factor VIII coagulant activity (FVIII:C). After purification the mutant FVIII was subjected to thrombin proteolysis, and was thereby activated 5.6-fold compared with 7-fold for wild type molecule. Subsequently, spontaneous inactivation of the mutant was much slower than noted for wild type FVIII. Western blot analysis using monoclonal antibodies demonstrated that thrombin cleavage of FVIII 373-Leu at positions 740 and 1689 were normal but that cleavage at position 372 was completely absent. Crystallographic coordinates of the active site of thrombin complexed to fibrinopeptide A were used to explore possible mechanistic reasons for the failure of thrombin to cleave the mutant FVIII at position 372. Steric hindrance between the mutant side chain and the side chain of the P1 residue was apparent. We conclude that the functional defect of FVIII 373-Leu results from the inability of thrombin to cleave the mutant at position 372-373, and propose that this is due to steric hindrance by the side chain of leucine 373, preventing correct formation of the enzyme substrate complex.

  3. Functional role of proteolytic cleavage at arginine-275 of human tissue plasminogen activator as assessed by site-directed mutagenesis

    International Nuclear Information System (INIS)

    Tate, K.M.; Higgins, D.L.; Holmes, W.E.; Winkler, M.E.; Heyneker, H.L.; Vehar, G.A.

    1987-01-01

    Activation of the zymogen form of a serine protease is associated with a conformational change that follows proteolysis at a specific site. Tissue-type plasminogen activator (t-PA) is homologous to mammalian serine proteases and contains an apparent activation cleavage site at arginine-275. To clarify the functional consequences of cleavage at arginine-275 of t-PA, site-specific mutagenesis was performed to convert arginine-275 to a glutamic acid. The mutant enzyme (designated Arg-275 → Glu t-PA) could be converted to the two-chain form by Staphylococcus aureus V8 protease but not by plasmin. The one-chain form was 8 times less active against the tripeptide substrate H-D-isoleucyl-L-prolyl-L-arginine-rho-nitroanilide (S-2288), and the ability of the enzyme to activate plasminogen in the absence of fibrinogen was reduced 20-50 times compared to the two-chain form. In contrast, one-chain Arg-275 → Glu t-PA has equal activity to the two-chain form when assayed in the presence of physiological levels of fibrinogen and plasminogen. Fibrin bound significantly more of the one-chain form of t-PA than the two-chain form for both the wild-type and mutated enzymes. One- and two-chain forms of the wild-type and mutated plasminogen activators slowly formed complexes with plasma protease inhibitors, although the one-chain forms showed decreased complex formation with → 2 -macroglobulin. The one-chain form of t-PA therefore is fully functional under physiologic conditions and has a increased fibrin binding compared to the two-chain form

  4. A Molecular Sensor To Characterize Arenavirus Envelope Glycoprotein Cleavage by Subtilisin Kexin Isozyme 1/Site 1 Protease

    Science.gov (United States)

    Oppliger, Joel; da Palma, Joel Ramos; Burri, Dominique J.; Khatib, Abdel-Majid; Spiropoulou, Christina F.

    2015-01-01

    ABSTRACT Arenaviruses are emerging viruses including several causative agents of severe hemorrhagic fevers in humans. The advent of next-generation sequencing technology has greatly accelerated the discovery of novel arenavirus species. However, for many of these viruses, only genetic information is available, and their zoonotic disease potential remains unknown. During the arenavirus life cycle, processing of the viral envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) is crucial for productive infection. The ability of newly emerging arenaviruses to hijack human SKI-1/S1P appears, therefore, to be a requirement for efficient zoonotic transmission and human disease potential. Here we implement a newly developed cell-based molecular sensor for SKI-1/S1P to characterize the processing of arenavirus GPC-derived target sequences by human SKI-1/S1P in a quantitative manner. We show that only nine amino acids flanking the putative cleavage site are necessary and sufficient to accurately recapitulate the efficiency and subcellular location of arenavirus GPC processing. In a proof of concept, our sensor correctly predicts efficient processing of the GPC of the newly emergent pathogenic Lujo virus by human SKI-1/S1P and defines the exact cleavage site. Lastly, we employed our sensor to show efficient GPC processing of a panel of pathogenic and nonpathogenic New World arenaviruses, suggesting that GPC cleavage represents no barrier for zoonotic transmission of these pathogens. Our SKI-1/S1P sensor thus represents a rapid and robust test system for assessment of the processing of putative cleavage sites derived from the GPCs of newly discovered arenavirus by the SKI-1/S1P of humans or any other species, based solely on sequence information. IMPORTANCE Arenaviruses are important emerging human pathogens that can cause severe hemorrhagic fevers with high mortality in humans. A crucial step in productive arenavirus

  5. Two tandem RNase III cleavage sites determine betT mRNA stability in response to osmotic stress in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Minji Sim

    Full Text Available While identifying genes regulated by ribonuclease III (RNase III in Escherichia coli, we observed that steady-state levels of betT mRNA, which encodes a transporter mediating the influx of choline, are dependent on cellular concentrations of RNase III. In the present study, we also observed that steady-state levels of betT mRNA are dependent on RNase III activity upon exposure to osmotic stress, indicating the presence of cis-acting elements controlled by RNase III in betT mRNA. Primer extension analyses of betT mRNA revealed two tandem RNase III cleavage sites in its stem-loop region, which were biochemically confirmed via in vitro cleavage assays. Analyses of cleavage sites suggested the stochastic selection of cleavage sites by RNase III, and mutational analyses indicated that RNase III cleavage at either site individually is insufficient for efficient betT mRNA degradation. In addition, both the half-life and abundance of betT mRNA were significantly increased in association with decreased RNase III activity under hyper-osmotic stress conditions. Our findings demonstrate that betT mRNA stability is controlled by RNase III at the post-transcriptional level under conditions of osmotic stress.

  6. Identification of the protease cleavage sites in a reconstituted Gag polyprotein of an HERV-K(HML-2 element

    Directory of Open Access Journals (Sweden)

    Kurth Reinhard

    2011-05-01

    Full Text Available Abstract Background The human genome harbors several largely preserved HERV-K(HML-2 elements. Although this retroviral family comes closest of all known HERVs to producing replication competent virions, mutations acquired during their chromosomal residence have rendered them incapable of expressing infectious particles. This also holds true for the HERV-K113 element that has conserved open reading frames (ORFs for all its proteins in addition to a functional LTR promoter. Uncertainty concerning the localization and impact of post-insertional mutations has greatly hampered the functional characterization of these ancient retroviruses and their proteins. However, analogous to other betaretroviruses, it is known that HERV-K(HML-2 virions undergo a maturation process during or shortly after release from the host cell. During this process, the subdomains of the Gag polyproteins are released by proteolytic cleavage, although the nature of the mature HERV-K(HML-2 Gag proteins and the exact position of the cleavage sites have until now remained unknown. Results By aligning the amino acid sequences encoded by the gag-pro-pol ORFs of HERV-K113 with the corresponding segments from 10 other well-preserved human specific elements we identified non-synonymous post-insertional mutations that have occurred in this region of the provirus. Reversion of these mutations and a partial codon optimization facilitated the large-scale production of maturation-competent HERV-K113 virus-like particles (VLPs. The Gag subdomains of purified mature VLPs were separated by reversed-phase high-pressure liquid chromatography and initially characterized using specific antibodies. Cleavage sites were identified by mass spectrometry and N-terminal sequencing and confirmed by mutagenesis. Our results indicate that the gag gene product Pr74Gag of HERV-K(HML-2 is processed to yield p15-MA (matrix, SP1 (spacer peptide of 14 amino acids, p15, p27-CA (capsid, p10-NC (nucleocapsid and two

  7. Identification of the protease cleavage sites in a reconstituted Gag polyprotein of an HERV-K(HML-2) element.

    Science.gov (United States)

    George, Maja; Schwecke, Torsten; Beimforde, Nadine; Hohn, Oliver; Chudak, Claudia; Zimmermann, Anja; Kurth, Reinhard; Naumann, Dieter; Bannert, Norbert

    2011-05-09

    The human genome harbors several largely preserved HERV-K(HML-2) elements. Although this retroviral family comes closest of all known HERVs to producing replication competent virions, mutations acquired during their chromosomal residence have rendered them incapable of expressing infectious particles. This also holds true for the HERV-K113 element that has conserved open reading frames (ORFs) for all its proteins in addition to a functional LTR promoter. Uncertainty concerning the localization and impact of post-insertional mutations has greatly hampered the functional characterization of these ancient retroviruses and their proteins. However, analogous to other betaretroviruses, it is known that HERV-K(HML-2) virions undergo a maturation process during or shortly after release from the host cell. During this process, the subdomains of the Gag polyproteins are released by proteolytic cleavage, although the nature of the mature HERV-K(HML-2) Gag proteins and the exact position of the cleavage sites have until now remained unknown. By aligning the amino acid sequences encoded by the gag-pro-pol ORFs of HERV-K113 with the corresponding segments from 10 other well-preserved human specific elements we identified non-synonymous post-insertional mutations that have occurred in this region of the provirus. Reversion of these mutations and a partial codon optimization facilitated the large-scale production of maturation-competent HERV-K113 virus-like particles (VLPs). The Gag subdomains of purified mature VLPs were separated by reversed-phase high-pressure liquid chromatography and initially characterized using specific antibodies. Cleavage sites were identified by mass spectrometry and N-terminal sequencing and confirmed by mutagenesis. Our results indicate that the gag gene product Pr74Gag of HERV-K(HML-2) is processed to yield p15-MA (matrix), SP1 (spacer peptide of 14 amino acids), p15, p27-CA (capsid), p10-NC (nucleocapsid) and two C-terminally encoded glutamine- and

  8. Identification of Cleavage Sites Recognized by the 3C-Like Cysteine Protease within the Two Polyproteins of Strawberry Mottle Virus

    Directory of Open Access Journals (Sweden)

    Hélène Sanfaçon

    2017-04-01

    Full Text Available Strawberry mottle virus (SMoV, family Secoviridae, order Picornavirales is one of several viruses found in association with strawberry decline disease in Eastern Canada. The SMoV genome consists of two positive-sense single-stranded RNAs, each encoding one large polyprotein. The RNA1 polyprotein (P1 includes the domains for a putative helicase, a VPg, a 3C-like cysteine protease and an RNA-dependent RNA polymerase at its C-terminus, and one or two protein domains at its N-terminus. The RNA2 polyprotein (P2 is predicted to contain the domains for a movement protein (MP and one or several coat proteins at its N-terminus, and one or more additional domains for proteins of unknown function at its C-terminus. The RNA1-encoded 3C-like protease is presumed to cleave the two polyproteins in cis (P1 and in trans (P2. Using in vitro processing assays, we systematically scanned the two polyproteins for cleavage sites recognized by this protease. We identified five cis-cleavage sites in P1, with cleavage between the putative helicase and VPg domains being the most efficient. The presence of six protein domains in the SMoV P1, including two upstream of the putative helicase domain, is a feature shared with nepoviruses but not with comoviruses. Results from trans-cleavage assays indicate that the RNA1-encoded 3C-like protease recognized a single cleavage site, which was between the predicted MP and coat protein domains in the P2 polyprotein. The cleavage site consensus sequence for the SMoV 3C-like protease is AxE (E or Q/(G or S.

  9. Defining a similarity threshold for a functional proteinsequence pattern: The signal peptide cleavage site

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engelbrecht, Jacob; von Heijne, Gunnar

    1996-01-01

    When preparing data sets of amino acid or nucleotide sequences it is necessary to exclude redundant or homologous sequences in order to avoid overestimating the predictive performance of an algorithm. For some time methods for doing this have been available in the area of protein structure...... prediction. We have developed a similar procedure based on pair-wise alignments for sequences with functional sites. We show how a correlation coefficient between sequence similarity and functional homology can be used to compare the efficiency of different similarity measures and choose a nonarbitrary...

  10. A consistency-based feature selection method allied with linear SVMs for HIV-1 protease cleavage site prediction.

    Directory of Open Access Journals (Sweden)

    Orkun Oztürk

    Full Text Available BACKGROUND: Predicting type-1 Human Immunodeficiency Virus (HIV-1 protease cleavage site in protein molecules and determining its specificity is an important task which has attracted considerable attention in the research community. Achievements in this area are expected to result in effective drug design (especially for HIV-1 protease inhibitors against this life-threatening virus. However, some drawbacks (like the shortage of the available training data and the high dimensionality of the feature space turn this task into a difficult classification problem. Thus, various machine learning techniques, and specifically several classification methods have been proposed in order to increase the accuracy of the classification model. In addition, for several classification problems, which are characterized by having few samples and many features, selecting the most relevant features is a major factor for increasing classification accuracy. RESULTS: We propose for HIV-1 data a consistency-based feature selection approach in conjunction with recursive feature elimination of support vector machines (SVMs. We used various classifiers for evaluating the results obtained from the feature selection process. We further demonstrated the effectiveness of our proposed method by comparing it with a state-of-the-art feature selection method applied on HIV-1 data, and we evaluated the reported results based on attributes which have been selected from different combinations. CONCLUSION: Applying feature selection on training data before realizing the classification task seems to be a reasonable data-mining process when working with types of data similar to HIV-1. On HIV-1 data, some feature selection or extraction operations in conjunction with different classifiers have been tested and noteworthy outcomes have been reported. These facts motivate for the work presented in this paper. SOFTWARE AVAILABILITY: The software is available at http

  11. The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Marie Trudel

    2016-01-01

    Full Text Available Polycystin-1 (PC1 plays an essential role in renal tubular morphogenesis, and PC1 dysfunction causes human autosomal dominant polycystic kidney disease. A fundamental characteristic of PC1 is post-translational modification via cleavage at the juxtamembrane GPCR proteolysis site (GPS motif that is part of the larger GAIN domain. Given the considerable biochemical complexity of PC1 molecules generated in vivo by this process, GPS cleavage has several profound implications on the intracellular trafficking and localization in association with their particular function. The critical nature of GPS cleavage is further emphasized by the increasing numbers of PKD1 mutations that significantly affect this cleavage process. The GAIN domain with the GPS motif therefore represents the key structural element with fundamental importance for PC1 and might be polycystic kidney disease’s (PKD Achilles’ heel in a large spectrum of PKD1 missense mutations. We highlight the central roles of PC1 cleavage for the regulation of its biogenesis, intracellular trafficking and function, as well as its significance in polycystic kidney disease.

  12. A catalytic metal ion interacts with the cleavage site G•U wobble in the HDV ribozyme†

    Science.gov (United States)

    Chen, Jui-Hui; Gong, Bo; Bevilacqua, Philip C.; Carey, Paul R.; Golden, Barbara L.

    2009-01-01

    The HDV ribozyme self-cleaves by a chemical mechanism involving general acid-base catalysis to generate a 2′,3′-cyclic phosphate and a 5′-hydroxyl termini. Biochemical studies from several laboratories have implicated C75 as the general acid and hydrated magnesium as the general base. We have previously shown that C75 has a pKa shifted > 2 pH units toward neutrality [Gong, B., Chen, J. H., Chase, E., Chadalavada, D. M., Yajima, R., Golden, B. L., Bevilacqua, P. C., and Carey, P. R. (2007) J. Am. Chem. Soc. 129, 13335–13342.], while in crystal structures, it is well-positioned for proton transfer. However no crystallographic evidence for a hydrated magnesium poised to serve as a general base in the reaction has been observed in high-resolution crystal structures of various reaction states and mutants. Herein, we use solution kinetic experiments and parallel Raman crystallographic studies to examine the effects of pH on rate and Mg2+-binding properties of wild-type and 7-deazaguanosine mutants of the HDV ribozyme. These data suggest that a previously-unobserved hydrated magnesium ion interacts with the N7 of the cleavage site G•U wobble base pair. Integrating this metal ion binding site with the available crystal structures provides a new three-dimensional model for the active site of the ribozyme that accommodates all available biochemical data and appears competent for catalysis. The position of this metal is consistent with a role of a magnesium-bound hydroxide as a general base as dictated by biochemical data. PMID:19178151

  13. Association between receptor protein-tyrosine phosphatase RPTPalpha and the Grb2 adaptor. Dual Src homology (SH) 2/SH3 domain requirement and functional consequences

    DEFF Research Database (Denmark)

    Su, J; Yang, L T; Sap, J

    1996-01-01

    domain in Grb2 (, ). We show here that association of Grb2 with RPTPalpha also involves a critical function for the C-terminal SH3 domain of Grb2. Furthermore, Grb2 SH3 binding peptides interfere with RPTPalpha-Grb2 association in vitro, and the RPTPalpha protein can dissociate the Grb2-Sos complex...... in vivo. These observations constitute a novel mode of Grb2 association and suggest a model in which association with a tyrosine-phosphorylated protein restricts the repertoire of SH3 binding proteins with which Grb2 can simultaneously interact. The function of the Tyr798 tyrosine phosphorylation/Grb2...... binding site in RPTPalpha was studied further by expression of wild type or mutant RPTPalpha proteins in PC12 cells. In these cells, wild type RPTPalpha interferes with acidic fibroblast growth factor-induced neurite outgrowth; this effect requires both the catalytic activity and the Grb2 binding Tyr798...

  14. Engineering D-Amino Acid Containing Collagen Like Peptide at the Cleavage Site of Clostridium histolyticum Collagenase for Its Inhibition.

    Directory of Open Access Journals (Sweden)

    Punitha Velmurugan

    Full Text Available Collagenase is an important enzyme which plays an important role in degradation of collagen in wound healing, cancer metastasis and even in embryonic development. However, the mechanism of this degradation has not yet been completely understood. In the field of biomedical and protein engineering, the design and development of new peptide based materials is of main concern. In the present work an attempt has been made to study the effect of DAla in collagen like peptide (imino-poor region of type I collagen on the structure and stability of peptide against enzyme hydrolysis. Effect of replacement of DAla in the collagen like peptide has been studied using circular dichroic spectroscopy (CD. Our findings suggest that, DAla substitution leads to conformational changes in the secondary structure and favours the formation of polyproline II conformation than its L-counterpart in the imino-poor region of collagen like peptides. Change in the chirality of alanine at the cleavage site of collagenase in the imino-poor region inhibits collagenolytic activity. This may find application in design of peptides and peptidomimics for enzyme-substrate interaction, specifically with reference to collagen and other extra cellular matrix proteins.

  15. Mutations near the cleavage site of enterocin NKR-5-3B prepeptide reveal new insights into its biosynthesis.

    Science.gov (United States)

    Perez, Rodney H; Sugino, Haruki; Ishibashi, Naoki; Zendo, Takeshi; Wilaipun, Pongtep; Leelawatcharamas, Vichien; Nakayama, Jiro; Sonomoto, Kenji

    2017-04-01

    Enterocin NKR-5-3B (Ent53B) is a 64-residue novel circular bacteriocin synthesized from an 87-residue prepeptide. Albeit through a still unknown mechanism, the EnkB1234 biosynthetic enzyme complex processes the prepeptide to yield its mature active, circular form. To gain insights into the key region/residue that plays a role in Ent53 maturation, several mutations near the cleavage site on the precursor peptide were generated. The interaction of the precursor peptide and EnkB1234 appeared to be hydrophobic in nature. At the Leu1 position, only mutations with helix structure-promoting hydrophobic residues (Ala, Ile, Val or Phe) were able to yield the mature Ent53B derivative. In this study, we also highlight the possible conformation-stabilizing role of the Ent53B leader peptide on the precursor peptide for its interaction with its biosynthetic enzyme complex. Any truncations of the leader peptide moiety interfered in the processing of the prepeptide. However, when propeptides of other circular bacteriocins (circularin A, leucocyclicin Q or lactocyclicin Q) were cloned at the C-terminus of the leader peptide, EnkB1234 could not process them to yield a mature bacteriocin. Taken together, these findings offer new perspectives in our understanding of the possible molecular mechanism of the biosynthesis of this circular bacteriocin. These new perspectives will help advance our current understanding to eventually elucidate circular bacteriocin biosynthesis. Understanding the biosynthetic mechanism of circular bacteriocins will materialize their application potential.

  16. Crystal structure of Bombyx mori arylphorins reveals a 3:3 heterohexamer with multiple papain cleavage sites

    Science.gov (United States)

    Hou, Yong; Li, Jianwei; Li, Yi; Dong, Zhaoming; Xia, Qingyou; Yuan, Y Adam

    2014-01-01

    In holometabolous insects, the accumulation and utilization of storage proteins (SPs), including arylphorins and methionine-rich proteins, are critical for the insect metamorphosis. SPs function as amino acids reserves, which are synthesized in fat body, secreted into the larval hemolymph and taken up by fat body shortly before pupation. However, the detailed molecular mechanisms of digestion and utilization of SPs during development are largely unknown. Here, we report the crystal structure of Bombyx mori arylphorins at 2.8 Å, which displays a heterohexameric structural arrangement formed by trimerization of dimers comprising two structural similar arylphorins. Our limited proteolysis assay and microarray data strongly suggest that papain-like proteases are the major players for B. mori arylphorins digestion in vitro and in vivo. Consistent with the biochemical data, dozens of papain cleavage sites are mapped on the surface of the heterohexameric structure of B. mori arylphorins. Hence, our results provide the insightful information to understand the metamorphosis of holometabolous insects at molecular level. PMID:24639361

  17. Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1-antitrypsin variants.

    Directory of Open Access Journals (Sweden)

    Anna Maisa

    2009-06-01

    Full Text Available Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication.We demonstrate that stable cell lines inducibly expressing S1P-adapted alpha(1-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of alpha(1-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific alpha(1-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different alpha(1-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor.Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.

  18. Disclosure of key stereoelectronic factors for efficient H2 binding and cleavage in the active site of [NiFe]-hydrogenases.

    Science.gov (United States)

    Bruschi, Maurizio; Tiberti, Matteo; Guerra, Alessandro; De Gioia, Luca

    2014-02-05

    A comparative analysis of a series of DFT models of [NiFe]-hydrogenases, ranging from minimal NiFe clusters to very large systems including both the first and second coordination sphere of the bimetallic cofactor, was carried out with the aim of unraveling which stereoelectronic properties of the active site of [NiFe]-hydrogenases are crucial for efficient H2 binding and cleavage. H2 binding to the Ni-SIa redox state is energetically favored (by 4.0 kcal mol(-1)) only when H2 binds to Ni, the NiFe metal cluster is in a low spin state, and the Ni cysteine ligands have a peculiar seesaw coordination geometry, which in the enzyme is stabilized by the protein environment. The influence of the Ni coordination geometry on the H2 binding affinity was then quantitatively evaluated and rationalized analyzing frontier molecular orbitals and populations. Several plausible reaction pathways leading to H2 cleavage were also studied. It turned out that a two-step pathway, where H2 cleavage takes place on the Ni-SIa redox state of the enzyme, is characterized by very low reaction barriers and favorable reaction energies. More importantly, the seesaw coordination geometry of Ni was found to be a key feature for facile H2 cleavage. The discovery of the crucial influence of the Ni coordination geometry on H2 binding and activation in the active site of [NiFe]-hydrogenases could be exploited in the design of novel biomimetic synthetic catalysts.

  19. Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia A.

    Science.gov (United States)

    Nguyen, G N; George, L A; Siner, J I; Davidson, R J; Zander, C B; Zheng, X L; Arruda, V R; Camire, R M; Sabatino, D E

    2017-01-01

    Essentials Factor (F) VIII is an inefficiently expressed protein. Furin deletion FVIII variants were purified and characterized using in vitro and in vivo assays. These minimally modified novel FVIII variants have enhanced function. These variants provide a strategy for increasing FVIII expression in hemophilia A gene therapy. Background The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a paired basic amino acid cleaving enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain-deleted (BDD) canine FVIII and hFVIII-R1645H, both differing from hFVIII by a single amino acid at this site, suggested that these proteins are secreted mainly in a single polypeptide chain (SC) form and exhibit enhanced function. Objective We hypothesized that deletion(s) of the furin site modulates FVIII biology and may enhance its function. Methods A series of recombinant hFVIII-furin deletion variants were introduced into hFVIII-BDD [Δ1645, 1645-46(Δ2), 1645-47(Δ3), 1645-48(Δ4), or Δ1648] and characterized. Results In vitro, recombinant purified Δ3 and Δ4 were primarily SC and, interestingly, had 2-fold higher procoagulant activity compared with FVIII-BDD. In vivo, the variants also have improved hemostatic function. After adeno-associated viral (AAV) vector delivery, the expression of these variants is 2-4-fold higher than hFVIII-BDD. Protein challenges of each variant in mice tolerant to hFVIII-BDD showed no anti-FVIII immune response. Conclusions These data suggest that the furin deletion hFVIII variants are superior to hFVIII-BDD without increased immunogenicity. In the setting of gene-based therapeutics, these novel variants provide a unique strategy to increase FVIII expression, thus lowering the vector dose, a

  20. UVES/VLT high resolution spectroscopy of GRB 050730 afterglow: probing the features of the GRB environment

    International Nuclear Information System (INIS)

    D'Elia, V.; Fiore, F.; Piranomonte, S.; Sbordone, L.; Stella, L.; Antonelli, L.A.; Fontana, A.; Giannini, T.; Guetta, D.; Israel, G.; Testa, V.; Meurs, E.J.A.; Vergani, S.D.; Ward, P.; Chincarini, G.; Tagliaferri, G.; Campana, S.; Fugazza, D.; Molinari, E.; Moretti, A.; Chincarini, G.; Melandri, A.; Norci, L.; Vergani, S.D.; Pellizza, L.; Filliatre, P.; Perna, R.; Lazzati, D.

    2007-01-01

    Aims. The aim of this paper is to study the Gamma Ray Burst (GRB) environment through the analysis of the optical absorption features due to the gas surrounding the GRB. Methods. To this purpose we analyze high resolution spectroscopic observations (R = 20000-45000, corresponding to 14 kms -1 at 4200 Angstroms and 6.6 kms -1 at 9000 Angstroms of the optical afterglow of GRB050730, obtained with UVES-VLT ∼ 4 h after the GRB trigger. Results. The spectrum shows that the ISM of the GRB host galaxy at z = 3.967 is complex, with at least five components contributing to the main absorption system. We detect strong CII*, SiII*, OI* and FeII* fine structure absorption lines associated to the second and third component. Conclusions. For the first three components we derive information on the relative distance from the site of the GRB explosion. Component 1, which has the longest wavelength, highest positive velocity shift, does not present any fine structure nor low ionization lines; it only shows very high ionization features, such as C IV and O VI, suggesting that this component is very close to the GRB site. From the analysis of low and high ionization lines and fine structure lines, we find evidences that the distance of component 2 from the site of the GRB explosion is 10-100 times smaller than that of component 3. We evaluated the mean metallicity of the z = 3.967 system obtaining values approximate to 10 -2 of the solar metallicity or less. However, this should not be taken as representative of the circum-burst medium, since the main contribution to the hydrogen column density comes from the outer regions of the galaxy while that of the other elements presumably comes from the ISM closer to the GRB site. Furthermore, difficulties in evaluating dust depletion correction can modify significantly these values. The mean [C/Fe] ratio agrees well with that expected by single star-formation event models. Interestingly the [C/Fe] of component 2 is smaller than that of

  1. Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases.

    OpenAIRE

    Schlaepfer, D D; Hunter, T

    1996-01-01

    Focal adhesion kinase (FAK) is a nonreceptor protein-tyrosine kinase (PTK) that associates with integrin receptors and participates in extracellular matrix-mediated signal transduction events. We showed previously that the c-Src nonreceptor PTK and the Grb2 SH2/SH3 adaptor protein bound directly to FAK after fibronectin stimulation (D. D. Schlaepfer, S.K. Hanks, T. Hunter, and P. van der Geer, Nature [London] 372:786-791, 1994). Here, we present evidence that c-Src association with FAK is req...

  2. Possible cleavage sites of glutelin partial degradation confirmed by immunological analysis in globulin-less mutants of rice (Oryza sativa L.).

    Science.gov (United States)

    Khan, Nadar; Yamaguchi, Satoru; Katsube-Tanaka, Tomoyuki

    2017-10-01

    Proteolytic cleavage or partial degradation of proteins is one of the important post-translational modifications for various biological processes, but it is difficult to analyze. Previously, we demonstrated that some subunits of the major rice (Oryza sativa L.) seed storage protein glutelin are partially degraded to produce newly identified polypeptides X1-X5 in mutants in which another major seed storage protein globulin is absent. In this study, the new polypeptides X3 and X4/X5 were immunologically confirmed to be derived from GluA3 and GluA1/GluA2 subunits, respectively. Additionally, the new polypeptides X1 and X2 were at least in part the α polypeptides of the GluB4 subunit partially degraded at the C-terminus. Simulated 2D-PAGE migration patterns of intact and partially degraded α polypeptides based on the calculation of their MWs and pIs enabled us to narrow or predict the possible locations of cleavage sites. The predicted cleavage sites were also verified by the comparison of 2D-PAGE patterns between seed-extracted and E. coli-expressed proteins of the intact and truncated α polypeptides. The results and methodologies demonstrated here would be useful for analyses of partial degradation of proteins and the structure-function relationships of rice seed protein bodies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. GRB 170817A: a short GRB seen off-axis

    Science.gov (United States)

    He, Xin-Bo; Tam, Pak-Hin Thomas; Shen, Rong-Feng

    2018-04-01

    The angular distribution of gamma-ray burst (GRB) jets is not yet clear. The observed luminosity of GRB 170817A is the lowest among all known short GRBs, which is best explained by the fact that our line of sight is outside of the jet opening angle, θ obs > θ j , where θ obs is the angle between our line of sight and the jet axis. As inferred by gravitational wave observations, as well as radio and X-ray afterglow modeling of GRB 170817A, it is likely that θ obs ∼ 20° – 28°. In this work, we quantitatively consider two scenarios of angular energy distribution of GRB ejecta: a top-hat jet and a structured jet with a power law index s. For the top-hat jet model, we get a large θ j (e.g., θ j > 10°), a rather high local (i.e., z 7.5 × 104, keV (∼500, keV for a typical short GRB). For the structured jet model, we use θ obs to give limits on s and θj for typical on-axis luminosity of a short GRB (e.g., 1049 erg s‑1 ∼ 1051 erg s‑1), and a low on-axis luminosity case (e.g., 1049 erg s‑1) gives more reasonable values of s. The structured jet model is more feasible for GRB 170817A than the top-hat jet model due to the rather high local short GRB rate, and the extremely high on-axis E peak,0 almost rules out the top-hat jet model. GRB 170817A is likely a low on-axis luminosity GRB (1049 erg s‑1) with a structured jet.

  4. Mapping DNA cleavage by the Type ISP restriction-modification enzymes following long-range communication between DNA sites in different orientations

    Science.gov (United States)

    van Aelst, Kara; Saikrishnan, Kayarat; Szczelkun, Mark D.

    2015-01-01

    The prokaryotic Type ISP restriction-modification enzymes are single-chain proteins comprising an Mrr-family nuclease, a superfamily 2 helicase-like ATPase, a coupler domain, a methyltransferase, and a DNA-recognition domain. Upon recognising an unmodified DNA target site, the helicase-like domain hydrolyzes ATP to cause site release (remodeling activity) and to then drive downstream translocation consuming 1–2 ATP per base pair (motor activity). On an invading foreign DNA, double-strand breaks are introduced at random wherever two translocating enzymes form a so-called collision complex following long-range communication between a pair of target sites in inverted (head-to-head) repeat. Paradoxically, structural models for collision suggest that the nuclease domains are too far apart (>30 bp) to dimerise and produce a double-strand DNA break using just two strand-cleavage events. Here, we examined the organisation of different collision complexes and how these lead to nuclease activation. We mapped DNA cleavage when a translocating enzyme collides with a static enzyme bound to its site. By following communication between sites in both head-to-head and head-to-tail orientations, we could show that motor activity leads to activation of the nuclease domains via distant interactions of the helicase or MTase-TRD. Direct nuclease dimerization is not required. To help explain the observed cleavage patterns, we also used exonuclease footprinting to demonstrate that individual Type ISP domains can swing off the DNA. This study lends further support to a model where DNA breaks are generated by multiple random nicks due to mobility of a collision complex with an overall DNA-binding footprint of ∼30 bp. PMID:26507855

  5. How Special Is GRB 170817A?

    Science.gov (United States)

    Yue, Chuan; Hu, Qian; Zhang, Fu-Wen; Liang, Yun-Feng; Jin, Zhi-Ping; Zou, Yuan-Chuan; Fan, Yi-Zhong; Wei, Da-Ming

    2018-01-01

    GRB 170817A is the first short gamma-ray burst (GRB) with direct detection of the gravitational-wave radiation and also the spectroscopically identified macronova emission (i.e., AT 2017gfo). The prompt emission of this burst, however, is underluminous in comparison with the other short GRBs with known redshift. In this work, we examine whether GRB 170817A is indeed unique. We first show that GRB 130603B/macronova may be the on-axis “analogs” of GRB 170817A/AT 2017gfo, and the extremely dim but long-lasting afterglow emission of GRB 170817A may suggest a low number density (∼ {10}-5 {{cm}}-3) of its circumburst medium and a structured outflow. We then discuss whether GRB 070923, GRB 080121, GRB 090417A, GRB 111005A, and GRB 170817A form a new group of very nearby underluminous GRBs originated from neutron star mergers. If the short events GRB 070923, GRB 080121, and GRB 090417A are indeed at a redshift of ∼ 0.076, 0.046, 0.088, respectively, their isotropic energies of the prompt emission are ∼ {10}47 erg and thus comparable to the other two events. The non-detection of optical counterparts of GRB 070923, GRB 080121, GRB 090417A, and GRB 111005A, however, strongly suggests that the macronovae from neutron star mergers are significantly diverse in luminosities or, alternatively, there is another origin channel (for instance, the white dwarf and black hole mergers). We finally suggest that GW170817/GRB 170817A are likely not alone and similar events will be detected by the upgraded/upcoming gravitational-wave detectors and the electromagnetic monitors.

  6. A Spatially Resolved Study of the GRB 020903 Host Galaxy

    Science.gov (United States)

    Thorp, Mallory D.; Levesque, Emily M.

    2018-03-01

    GRB 020903 is a long-duration gamma-ray burst with a host galaxy close enough and extended enough for spatially resolved observations, making it one of less than a dozen GRBs where such host studies are possible. GRB 020903 lies in a galaxy host complex that appears to consist of four interacting components. Here we present the results of spatially resolved spectroscopic observations of the GRB 020903 host. By taking observations at two different position angles, we were able to obtain optical spectra (3600–9000 Å) of multiple regions in the galaxy. We confirm redshifts for three regions of the host galaxy that match that of GRB 020903. We measure the metallicity of these regions, and find that the explosion site and the nearby star-forming regions both have comparable subsolar metallicities. We conclude that, in agreement with past spatially resolved studies of GRBs, the GRB explosion site is representative of the host galaxy as a whole rather than localized in a metal-poor region of the galaxy.

  7. Fluorescence quenching of graphene oxide combined with the site-specific cleavage of restriction endonuclease for deoxyribonucleic acid demethylase activity assay

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Lijuan; Qian, Yingdan; Wu, Ping; Zhang, Hui; Cai, Chenxin, E-mail: cxcai@njnu.edu.cn

    2015-04-15

    Highlights: • An approach for sensitive and selective DNA demethylase activity assay is reported. • This assay is based on the fluorescence quenching of GO and site-specific cleavage of endonuclease. • It can determine as low as 0.05 ng mL{sup −1} of MBD2 with a linear range of 0.2–300 ng mL{sup −1}. • It has an ability to recognize MBD2 from other possibly coexisting proteins and cancer cell extracts. • It can avoid false signals, requiring no bisulfite conversion, PCR amplification, radioisotope-labeling. - Abstract: We report on the development of a sensitive and selective deoxyribonucleic acid (DNA) demethylase (using MBD2 as an example) activity assay by coupling the fluorescence quenching of graphene oxide (GO) with the site-specific cleavage of HpaII endonuclease to improve the selectivity. This approach was developed by designing a single-stranded probe (P1) that carries a binding region to facilitate the interaction with GO, which induces fluorescence quenching of the labeled fluorophore (FAM, 6-carboxyfluorescein), and a sensing region, which contains a hemi-methylated site of 5′-CmCGG-3′, to specifically recognize the target (T1, a 32-mer DNA from the promoter region of p53 gene) and hybridize with it to form a P1/T1 duplex. After demethylation with MBD2, the duplex can be specifically cleaved using HpaII, which releases the labeled FAM from the GO surface and results in the recovery of fluorescence. However, this cleavage is blocked by the hemi-methylation of this site. Thus, the magnitude of the recovered fluorescence signal is related to the MBD2 activity, which establishes the basis of the DNA demethylase activity assay. This assay can determine as low as ∼(0.05 ± 0.01) ng mL{sup −1} (at a signal/noise of 3) of MBD2 with a linear range of 0.2–300 ng mL{sup −1} and recognize MBD2 from other possibly coexisting proteins and cancer cell extracts. The advantage of this assay is its ability to avoid false signals and no

  8. The latest two GRB detected by Hete-2: GRB 051022 and GRB 051028

    International Nuclear Information System (INIS)

    Castro-Tirado, A. J.; Jelinek, M.; Pandey, S. B.; Ugarte Postigo, A. de; Gorosabel, J.; McBreen, S.; Bremer, M.; Guziy, S.; Bihain, G.; Caballero, J. A.; Ferrero, P.; Jong, J de; Misra, K.; Sahu, D. K.

    2006-01-01

    We present multiwavelength observations of the latest two GRB detected by Hete-2 in 2005. For GRB 051022, no optical/nIR afterglow has been detected, in spite of the strong gamma-ray emission and the reported X-ray afterglow discovered by Swift. A mm afterglow was discovered at PdB confirming the association of this event with a luminous (MV = - 21.5) galaxy within the X-ray error box. Spectroscopy of this galaxy shows strong a strong [O II] emission line at z = 0.807, besides weaker [O III] emission. The X-ray spectrum showed evidence of considerable absorption by neutral gas with NH,X-ray = 4.5 x 1022 cm2 (at rest frame). ISM absorption by dust in the host galaxy at z = 0.807 cannot certainly account for the non-detection of the optical afterglow, unless the dust-to-gas ratio is quite different than that seen in our Galaxy. It is possible then that GRB 051022 was produced in an obscured, stellar forming region in its parent host galaxy.For GRB 051028, the data can be interpreted by collimated emission (a jet model with p = 2.4) moving in an homogeneous ISM and with a cooling frequency vc still above the X-rays at 0.5 days after the burst onset. GRB 051028 can be classified as a 'gray' or 'potentially dark' GRB. The Swift/XRT data are consistent with the interpretation that the reason for the optical dimness is not extra absorption in the host galaxy, but rather the GRB taking place at high-redshift

  9. The Macronova in GRB 050709 and the GRB-macronova connection

    Science.gov (United States)

    Jin, Zhi-Ping; Hotokezaka, Kenta; Li, Xiang; Tanaka, Masaomi; D'Avanzo, Paolo; Fan, Yi-Zhong; Covino, Stefano; Wei, Da-Ming; Piran, Tsvi

    2016-01-01

    GRB 050709 was the first short Gamma-ray Burst (sGRB) with an identified optical counterpart. Here we report a reanalysis of the publicly available data of this event and the discovery of a Li-Paczynski macronova/kilonova that dominates the optical/infrared signal at t>2.5 days. Such a signal would arise from 0.05 r-process material launched by a compact binary merger. The implied mass ejection supports the suggestion that compact binary mergers are significant and possibly main sites of heavy r-process nucleosynthesis. Furthermore, we have reanalysed all afterglow data from nearby short and hybrid GRBs (shGRBs). A statistical study of shGRB/macronova connection reveals that macronova may have taken place in all these GRBs, although the fraction as low as 0.18 cannot be ruled out. The identification of two of the three macronova candidates in the I-band implies a more promising detection prospect for ground-based surveys. PMID:27659791

  10. GRB 030227: The first multiwavelength afterglow of an INTEGRAL GRB

    DEFF Research Database (Denmark)

    Castro-Tirado, A.J.; Gorosabel, J.; Guziy, S.

    2003-01-01

    We present multiwavelength observations of a gamma-ray burst detected by INTEGRAL (GRB 030227) between 5.3 hours and similar to1.7 days after the event. Here we report the discovery of a dim optical afterglow (OA) that would not have been detected by many previous searches due to its faintess (R ...

  11. Grb7 binds to Hax-1 and undergoes an intramolecular domain association that offers a model for Grb7 regulation

    OpenAIRE

    Siamakpour-Reihani, Sharareh; Peterson, Tabitha A.; Bradford, Andrew M.; Argiros, Haroula J.; Haas, Laura Lowell; Lor, Siamee N.; Haulsee, Zachary M.; Spuches, Anne M.; Johnson, Dennis L.; Rohrschneider, Larry R.; Shuster, Charles Brad; Lyons, Barbara A.

    2011-01-01

    Adaptor proteins mediate signal transduction from cell surface receptors to downstream signaling pathways. The Grb7 protein family of adaptor proteins is constituted by Grb7, Grb10, and Grb14. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7-mediated cell migration has been shown to proceed through a focal adhesion kinase (FAK)/Grb7 pathway, although the specific participants downstream of Grb7 in cell migration signaling have not been full...

  12. Beneficial effect of antibodies against β- secretase cleavage site of APP on Alzheimer's-like pathology in triple-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Inna Rabinovich-Nikitin

    Full Text Available The toxicity of amyloid β and tau, the two hallmark proteins in Alzheimer's disease (AD, has been extensively studied individually. Recently new data suggest their possible interactions and synergistic effects in the disease. In this study, we investigate the ability of antibodies against the β secretase cleavage site on APP, named BBS1, to affect tau pathology, besides their well established effect on intracellular Aβ and amyloid load. For this purpose we treated the triple transgenic mice model of AD (3x Tg-AD with mAb BBS1 intracerebroventricularly, using mini osmotic pumps for one month. The experimental data demonstrated reduction in total and phosphorylated tau levels, explained by significant reduction in GSK3β which phosphorylates tau on sites recognized by antibodies against PHF1 and AT-8. The treatment increased the cognitive capabilities and reduced the brain inflammation levels which accompany AD pathology. The data showing that tau pathology was significantly reduced by BBS1 antibodies suggest a close interaction between tau and Aβ in the development of AD, and may serve as an efficient novel immunotherapy against both hallmarks of this disease.

  13. Albumin Redhill (-1 Arg, 320 Ala → Thr): A glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site

    International Nuclear Information System (INIS)

    Brennan, S.O.; Myles, T.; Peach, R.J.; George, P.M.; Donaldson, D.

    1990-01-01

    Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63 Ni 2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni 2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis of the genetic variation or the increase in apparent molecular mass. Fractionation of tryptic digests on concanavalin A-Sepharose followed by peptide mapping of the bound and unbound fractions and sequence analysis of the glycopeptides identified a mutation of 320 Ala → Thr. This introduces as Asn-Tyr-Thr oligosaccharide attachment sequence centered on Asn-318 and explains the increase in molecular mass. This, however, did not satisfactorily explain the presence of the additional Arg residue at position -1. DNA sequencing of polymerase chain reaction-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation of -2 Arg → Cys. The authors propose that the new Phe-Cys-Arg sequence in the propeptide is an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, the site of the diarginyl-specific proalbumin convertase

  14. Deletion of the calmodulin-binding domain of Grb7 impairs cell attachment to the extracellular matrix and migration

    Energy Technology Data Exchange (ETDEWEB)

    García-Palmero, Irene; Villalobo, Antonio, E-mail: antonio.villalobo@iib.uam.es

    2013-06-28

    Highlights: •Grb7 is a calmodulin (CaM)-binding protein. •Deleting the CaM-binding site impairs cell attachment and migration. •CaM antagonists inhibit Grb7-mediated cell migration. •We conclude that CaM controls Grb7-mediated cell migration. -- Abstract: The adaptor Grb7 is a calmodulin (CaM)-binding protein that participates in signaling pathways involved in cell migration, proliferation and the control of angiogenesis, and plays a significant role in tumor growth, its metastatic spread and tumor-associated neo-vasculature formation. In this report we show that deletion of the CaM-binding site of Grb7, located in the proximal region of its pleckstrin homology (PH) domain, impairs cell migration, cell attachment to the extracellular matrix, and the reorganization of the actin cytoskeleton occurring during this process. Moreover, we show that the cell-permeable CaM antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide (W-13) both retard the migration of cells expressing wild type Grb7, but not the migration of cells expressing the mutant protein lacking the CaM-binding site (Grb7Δ), underscoring the proactive role of CaM binding to Grb7 during this process.

  15. Group I-like ribozymes with a novel core organization perform obligate sequential hydrolytic cleavages at two processing sites

    DEFF Research Database (Denmark)

    Einvik, C; Nielsen, Henrik; Westhof, E

    1998-01-01

    A new category of self-splicing group I introns with conserved structural organization and function is found among the eukaryotic microorganisms Didymium and Naegleria. These complex rDNA introns contain two distinct ribozymes with different functions: a regular group I splicing...... available GIR1 sequences and propose a common RNA secondary structure resembling that of group I splicing-ribozymes, but with some important differences. The GIR1s lack most peripheral sequence components, as well as a P1 segment, and, at approximately 160-190 nt, they are the smallest functional group I...... ribozymes known from nature. All GIR1s were found to contain a novel 6-bp pseudoknot (P15) within their catalytic core region. Experimental support of the proposed structure was obtained from the Didymium GIR1 by RNA structure probing and site-directed mutagenesis. Three-dimensional modeling indicates...

  16. Systematic Design of Trypsin Cleavage Site Mutated Exendin4-Cysteine 1, an Orally Bioavailable Glucagon-Like Peptide-1 Receptor Agonist

    Directory of Open Access Journals (Sweden)

    Wenbo Sai

    2017-03-01

    Full Text Available Exendin-4 is a strong therapeutic candidate for the treatment of metabolic syndrome. Related receptor agonist drugs have been on the market since 2005. However, technical limitations and the pain caused by subcutaneous injection have severely limited patient compliance. The goal of the study is to investigate a biologically active exendin-4 analog could be administered orally. Using intraperitoneal glucose tolerance tests, we discovered that exendin4-cysteine administered by oral gavage had a distinct hypoglycemic effect in C57BL/6J mice. Using Rosetta Design and Amber, we designed and screened a series of exendin4-cysteine analogs to identify those that retained biological activity while resisting trypsin digestion. Trypsin Cleavage Site Mutated Exendin4-cysteine 1 (TSME-1, an analog whose bioactivity was similar to exendin-4 and was almost completely resistant to trypsin, was screened out. In addition, TSME-1 significantly normalized the blood glucose levels and the availability of TSME-1 was significantly higher than that of exendin-4 and exendin4-cysteine. Collectively orally administered TSME-1, a trypsin-resistant exendin-4 analog obtained by the system, is a strong candidate for future treatments of type 2 diabetes.

  17. Mutation in the protease cleavage site of GDF9 increases ovulation rate and litter size in heterozygous ewes and causes infertility in homozygous ewes.

    Science.gov (United States)

    Souza, C J H; McNeilly, A S; Benavides, M V; Melo, E O; Moraes, J C F

    2014-10-01

    Litter size (LS) in sheep is determined mainly by ovulation rate (OR). Several polymorphisms have been identified in the growth differentiation factor 9 (GDF9) gene that result in an increase in OR and prolificacy of sheep. Screening the databank of the Brazilian Sheep Breeders Association for triplet delivery, we identified flocks of prolific Ile de France ewes. After resequencing of GDF9, a point mutation (c.943C>T) was identified, resulting in a non-conservative amino acid change (p.Arg315Cys) in the cleavage site of the propeptide. This new allele was called Vacaria (FecG(v) ). A flock of half-sib ewes was evaluated for OR in the first three breeding seasons, and Vacaria heterozygotes had higher OR (P develop up to small antral stages, although with abnormal oocyte morphology and altered arrangement of granulosa cells. After the collapse of the oocyte in most follicles, the remaining cells formed clusters that persisted in the ovary. This SNP is useful to improve selection for dam prolificacy and also as a model to investigate GDF9 post-translation processing and the fate of the follicular cells that remain after the oocyte demise. © 2014 Stichting International Foundation for Animal Genetics.

  18. VLT/X-shooter spectroscopy of the GRB 120327A afterglow

    DEFF Research Database (Denmark)

    D'Elia, V.; Fynbo, Johan Peter Uldall; Goldoni, P.

    2014-01-01

    we used to derive information on the distance between the host absorbing gas and the site of the GRB explosion. The variability of the FeI\\lambda2396 excited line between the two epochs proves that these features are excited by the GRB UV flux. Moreover, the distance of component I is found to be d......I=200+100-60 pc, while component II is located closer to the GRB, at dII=100+40-30 pc. These values are among the lowest found in GRBs. Component III does not show excited transitions, so it should be located farther away from the GRB. The presence of H2 molecules is firmly established, with a molecular...

  19. [Prokaryotic expression and immunogenicity analysis of the chimeric HBcAg containing APP beta cleavage site peptide and Aβ(1-15);].

    Science.gov (United States)

    Feng, Gai-feng; Wang, Jun-yang; Jin, Hui; Wang, Wei-xi; Qian, Yi-hua; Yang, Wei-na; Wang, Quan-ying; Yang, Guang-xiao

    2011-11-01

    To construct the recombinant prokaryotic expression plasmid pET/c-ABCSP-Aβ(15-c);, and evaluate the immunogenicity of the fusion protein expressed in E.coli. The gene fragment HBc88-144 was amplified by PCR and subcloned to pUC19. The APP beta cleavage site peptide(ABCSP) and Aβ(1-15); gene(ABCSP-Aβ(15);) was amplified by PCR and inserted downstream of HBc1-71 in pGEMEX/c1-71. After restriction enzyme digestion, c1-17-ABCSP-Aβ(15); were connected with HBc88-144, yielding the recombinant gene c-ABCSP-Aβ(15-c);. c-ABCSP-Aβ(15-c); gene was subcloned into pET-28a(+).The fusion protein expressed in transformed E.coli BL21 was induced with IPTG and analyzed by SDS-PAGE. The virus-like particles (VLP) formed by fusion protein was observed with Transmission Electron Microscope (TEM). 4 Kunming (KM) mice received intraperitoneal injection (i.p) of fusion protein VLP. The antibody was detected by indirect ELISA. The recombinant gene was confirmed by restriction enzyme digestion and DNA sequencing. After IPTG induction, fusion protein was expressed and mainly existed in the sediment of the bacterial lysate. The expression level was 40% of all the proteins in the sediment. The fusion protein could form VLP. After 5 times of immunization, the titer of anti-ABCSP and anti-Aβantibody in sera of KM mice reached up to 1:5 000 and 1:10 000 respectively, while the anti-HBc antibody was undetectable. Recombinant c-ABCSP-Aβ(15-c); gene can be expressed in E.coli. The expressed protein could form VLP and has a strong immunogenicity. This study lays the foundation for the study of AD genetic engineering vaccine.

  20. Study of WATCH GRB error boxes

    DEFF Research Database (Denmark)

    Gorosabel, J.; Castro-Tirado, A. J.; Lund, Niels

    1995-01-01

    We have studied the first WATCH GRB Catalogue ofγ-ray Bursts in order to find correlations between WATCH GRB error boxes and a great variety of celestial objects present in 33 different catalogues. No particular class of objects has been found to be significantly correlated with the WATCH GRBs....

  1. In vitro maturation of Drosophila melanogaster Spätzle protein with refolded Easter reveals a novel cleavage site within the prodomain.

    Science.gov (United States)

    Ursel, Christian; Fandrich, Uwe; Hoffmann, Anita; Sieg, Torsten; Ihling, Christian; Stubbs, Milton T

    2013-08-01

    Dorsoventral patterning during Drosophila melanogaster embryogenesis is mediated by a well-defined gradient of the mature NGF-like ligand Spätzle. Easter, the ultimate protease of a ventrally-restricted serine protease cascade, plays a key role in the regulation of the morphogenic gradient, catalyzing the activation cleavage of proSpätzle. As a result of alternative splicing, proSpätzle exists in multiple isoforms, almost all of which differ only in their prodomain. Although this domain is unstructured in isolation, it has a stabilizing influence on the mature cystine knot domain and is involved in the binding to the Toll receptor. Here, we report the expression and refolding of Easter, and show that the renatured enzyme performs the activation cleavage of two Spätzle isoforms. We determine the affinity of the prodomain for the cystine knot domain, and show that Easter performs a previously unknown secondary cleavage in each prodomain.

  2. The ultraluminous GRB 110918A

    International Nuclear Information System (INIS)

    Frederiks, D. D.; Svinkin, D. S.; Pal'shin, V. D.; Aptekar, R. L.; Golenetskii, S. V.; Mazets, E. P.; Oleynik, Ph. P.; Tsvetkova, A. E.; Ulanov, M. V.; Kokomov, A. A.; Hurley, K.; Mangano, V.; Burrows, D. N.; Sbarufatti, B.; Siegel, M. H.; Oates, S.; Cline, T. L.; Krimm, H. A.; Pagani, C.; Mitrofanov, I. G.

    2013-01-01

    GRB 110918A is the brightest long gamma-ray burst (GRB) detected by Konus-WIND during its almost 19 yr of continuous observations and the most luminous GRB ever observed since the beginning of the cosmological era in 1997. We report on the final Interplanetary Network localization of this event and its detailed multiwavelength study with a number of space-based instruments. The prompt emission is characterized by a typical duration, a moderate peak energy of the time-integrated spectrum, and strong hard-to-soft evolution. The high observed energy fluence yields, at z = 0.984, a huge isotropic-equivalent energy release E iso = (2.1 ± 0.1) × 10 54 erg. The record-breaking energy flux observed at the peak of the short, bright, hard initial pulse results in an unprecedented isotropic-equivalent luminosity L iso = (4.7 ± 0.2) × 10 54 erg s –1 . A tail of the soft γ-ray emission was detected with temporal and spectral behavior typical of that predicted by the synchrotron forward-shock model. The Swift/X-Ray Telescope and the Swift/Ultraviolet Optical Telescope observed the bright afterglow from 1.2 to 48 days after the burst and revealed no evidence of a jet break. The post-break scenario for the afterglow is preferred from our analysis, with a hard underlying electron spectrum and interstellar-medium-like circumburst environment implied. We conclude that, among the multiple reasons investigated, the tight collimation of the jet must have been a key ingredient to produce this unusually bright burst. The inferred jet opening angle of 1.°7-3.°4 results in reasonable values of the collimation-corrected radiated energy and the peak luminosity, which, however, are still at the top of their distributions for such tightly collimated events. We estimate a detection horizon for a similar ultraluminous GRB of z ∼ 7.5 for Konus-WIND and z ∼ 12 for the Swift/Burst Alert Telescope, which stresses the importance of GRBs as probes of the early Universe.

  3. Human adenovirus serotype 12 virion precursors pMu and pVI are cleaved at amino-terminal and carboxy-terminal sites that conform to the adenovirus 2 endoproteinase cleavage consensus sequence.

    Science.gov (United States)

    Freimuth, P; Anderson, C W

    1993-03-01

    The sequence of a 1158-base pair fragment of the human adenovirus serotype 12 (Ad12) genome was determined. This segment encodes the precursors for virion components Mu and VI. Both Ad12 precursors contain two sequences that conform to a consensus sequence motif for cleavage by the endoproteinase of adenovirus 2 (Ad2). Analysis of the amino terminus of VI and of the peptide fragments found in Ad12 virions demonstrated that these sites are cleaved during Ad12 maturation. This observation suggests that the recognition motif for adenovirus endoproteinases is highly conserved among human serotypes. The adenovirus 2 endoproteinase polypeptide requires additional co-factors for activity (C. W. Anderson, Protein Expression Purif., 1993, 4, 8-15). Synthetic Ad12 or Ad2 pVI carboxy-terminal peptides each permitted efficient cleavage of an artificial endoproteinase substrate by recombinant Ad2 endoproteinase polypeptide.

  4. THE PROMPT, HIGH-RESOLUTION SPECTROSCOPIC VIEW OF THE 'NAKED-EYE' GRB080319B

    International Nuclear Information System (INIS)

    D'Elia, V.; Fiore, F.; Nicastro, F.; Antonelli, L. A.; Guetta, D.; Perna, R.; Lazzati, D.; Krongold, Y.; Covino, S.; Fugazza, D.; Campana, S.; Chincarini, G.; D'Avanzo, P.; Guidorzi, C.; Molinari, E.; Valle, M. Della; Goldoni, P.; Meurs, E. J. A.; Mirabel, F.; Norci, L.

    2009-01-01

    GRB080319B reached fifth optical magnitude during the burst prompt emission. Thanks to the Very Large Telescope (VLT)/Ultraviolet and Visual Echelle Spectrograph (UVES) rapid response mode, we observed its afterglow just 8m:30s after the gamma-ray burst (GRB) onset when the magnitude was R ∼ 12. This allowed us to obtain the best signal-to-noise (S/N), high-resolution spectrum of a GRB afterglow ever (S/N per resolution element ∼50). The spectrum is rich of absorption features belonging to the main system at z = 0.937, divided in at least six components spanning a total velocity range of 100 km s -1 . The VLT/UVES observations caught the absorbing gas in a highly excited state, producing the strongest Fe II fine structure lines ever observed in a GRB. A few hours later, the optical depth of these lines was reduced by a factor of 4-20, and the optical/UV flux by a factor of ∼60. This proves that the excitation of the observed fine structure lines is due to 'pumping' by the GRB UV photons. A comparison of the observed ratio between the number of photons absorbed by the excited state and those in the Fe II ground state suggests that the six absorbers are ∼2-6 kpc from the GRB site, with component I ∼ 3 times closer to the GRB site than components III-VI. Component I is characterized also by the lack of Mg I absorption, unlike all other components. This may be both due to a closer distance and a lower density, suggesting a structured interstellar matter in this galaxy complex.

  5. Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation

    Directory of Open Access Journals (Sweden)

    Pero Stephanie C

    2007-09-01

    Full Text Available Abstract Background Human growth factor receptor bound protein 7 (Grb7 is an adapter protein that mediates the coupling of tyrosine kinases with their downstream signaling pathways. Grb7 is frequently overexpressed in invasive and metastatic human cancers and is implicated in cancer progression via its interaction with the ErbB2 receptor and focal adhesion kinase (FAK that play critical roles in cell proliferation and migration. It is thus a prime target for the development of novel anti-cancer therapies. Recently, an inhibitory peptide (G7-18NATE has been developed which binds specifically to the Grb7 SH2 domain and is able to attenuate cancer cell proliferation and migration in various cancer cell lines. Results As a first step towards understanding how Grb7 may be inhibited by G7-18NATE, we solved the crystal structure of the Grb7 SH2 domain to 2.1 Å resolution. We describe the details of the peptide binding site underlying target specificity, as well as the dimer interface of Grb 7 SH2. Dimer formation of Grb7 was determined to be in the μM range using analytical ultracentrifugation for both full-length Grb7 and the SH2 domain alone, suggesting the SH2 domain forms the basis of a physiological dimer. ITC measurements of the interaction of the G7-18NATE peptide with the Grb7 SH2 domain revealed that it binds with a binding affinity of Kd = ~35.7 μM and NMR spectroscopy titration experiments revealed that peptide binding causes perturbations to both the ligand binding surface of the Grb7 SH2 domain as well as to the dimer interface, suggesting that dimerisation of Grb7 is impacted on by peptide binding. Conclusion Together the data allow us to propose a model of the Grb7 SH2 domain/G7-18NATE interaction and to rationalize the basis for the observed binding specificity and affinity. We propose that the current study will assist with the development of second generation Grb7 SH2 domain inhibitors, potentially leading to novel inhibitors of

  6. The MUSE view of the host galaxy of GRB 100316D

    Science.gov (United States)

    Izzo, L.; Thöne, C. C.; Schulze, S.; Mehner, A.; Flores, H.; Cano, Z.; de Ugarte Postigo, A.; Kann, D. A.; Amorín, R.; Anderson, J. P.; Bauer, F. E.; Bensch, K.; Christensen, L.; Covino, S.; Della Valle, M.; Fynbo, J. P. U.; Jakobsson, P.; Klose, S.; Kuncarayakti, H.; Leloudas, G.; Milvang-Jensen, B.; Møller, P.; Puech, M.; Rossi, A.; Sánchez-Ramírez, R.; Vergani, S. D.

    2017-12-01

    The low distance, z = 0.0591, of GRB 100316D and its association with SN 2010bh represent two important motivations for studying this host galaxy and the GRB's immediate environment with the integral field spectrographs like Very Large Telescope/Multi-Unit Spectroscopic Explorer. Its large field of view allows us to create 2D maps of gas metallicity, ionization level and the star formation rate (SFR) distribution maps, as well as to investigate the presence of possible host companions. The host is a late-type dwarf irregular galaxy with multiple star-forming regions and an extended central region with signatures of on-going shock interactions. The gamma-ray burst (GRB) site is characterized by the lowest metallicity, the highest SFR and the youngest (∼20-30 Myr) stellar population in the galaxy, which suggest a GRB progenitor stellar population with masses up to 20-40 M⊙. We note that the GRB site has an offset of ∼660 pc from the most luminous SF region in the host. The observed SF activity in this galaxy may have been triggered by a relatively recent gravitational encounter between the host and a small undetected (LH α ≤ 1036 erg s-1) companion.

  7. In vivo analysis of the Notch receptor S1 cleavage.

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    2009-08-01

    Full Text Available A ligand-independent cleavage (S1 in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control.

  8. Tyrosine phosphorylation of Grb14 by Tie2

    Directory of Open Access Journals (Sweden)

    Dumont Daniel J

    2010-10-01

    Full Text Available Abstract Background Growth factor receptor bound (Grb proteins 7, 10 and 14 are a family of structurally related multi-domain adaptor proteins involved in a variety of biological processes. Grb7, 10 and 14 are known to become serine and/or threonine phosphorylated in response to growth factor (GF stimulation. Grb7 and 10 have also been shown to become tyrosine phosphorylated under certain conditions. Under experimental conditions Grb7 is tyrosine phosphorylated by the Tie2/Tie-2/Tek angiogenic receptor tyrosine kinase (RTK. Furthermore, Grb14 has also been shown to interact with Tie2, however tyrosine phosphorylation of this Grb family member has yet to be reported. Results Here we report for the first time tyrosine phosphorylation of Grb14. This phosphorylation requires a kinase competent Tie2 as well as intact tyrosines 1100 and 1106 (Y1100 and Y1106 on the receptor. Furthermore, a complete SH2 domain on Grb14 is required for Grb14 tyrosine phosphorylation by Tie2. Grb14 was also able to become tyrosine phosphorylated in primary endothelial cells when treated with a soluble and potent variant of the Tie2 ligand, cartilage oligomeric matrix protein (COMP Ang1. Conclusion Our results show that Grb14, like its family members Grb7 and Grb10, is able to be tyrosine phosphorylated. Furthermore, our data indicate a role for Grb14 in endothelial signaling downstream of the Tie2 receptor.

  9. Search algorithm for a gravitational wave signal in association with gamma ray burst GRB030329 using the LIGO detectors

    International Nuclear Information System (INIS)

    Mohanty, S D; Marka, Sz; Rahkola, R; Mukherjee, S; Leonor, I; Frey, R; Cannizzo, J; Camp, J

    2004-01-01

    One of the brightest gamma ray bursts ever recorded, GRB030329, occurred during the second science run of the LIGO detectors. At that time, both interferometers at the Hanford, WA LIGO site were in lock and were acquiring data. The data collected from the two Hanford detectors were analysed for the presence of a gravitational wave signal associated with this GRB. This paper presents a detailed description of the search algorithm implemented in the current analysis

  10. GRB 111005A at z = 0.0133 and the Prospect of Establishing Long-Short GRB/GW Association

    Science.gov (United States)

    Wang, Yuan-Zhu; Huang, Yong-Jia; Liang, Yun-Feng; Li, Xiang; Jin, Zhi-Ping; Zhang, Fu-Wen; Zou, Yuan-Chuan; Fan, Yi-Zhong; Wei, Da-Ming

    2017-12-01

    GRB 111005A, a long-duration gamma-ray burst (GRB) that occurred within a metal-rich environment that lacks massive stars with {M}{ZAMS}≥slant 15 {M}⊙ , is not coincident with supernova emission down to a stringent limit and thus should be classified as a “long-short” GRB (lsGRB; also known as an SN-less long GRB or hybrid GRB), like GRB 060505 and GRB 060614. In this work, we show that in the neutron star merger model the non-detection of the optical/infrared emission of GRB 111005A requires sub-relativistic neutron-rich ejecta with a mass of ≤slant 0.01 {M}⊙ , which is (significantly) less massive than that of GRB 130603B, GRB 060614, GRB 050709, and GRB 170817A. The lsGRBs are found to have a high rate density and the neutron star merger origin model can be unambiguously tested by the joint observations of the second-generation gravitational-wave (GW) detectors and the full-sky gamma-ray monitors such as Fermi-GBM and the proposed GECAM. If no lsGRB/GW association is observed in the 2020s, alternative scenarios have to be systematically investigated. With the detailed environmental information achievable for the nearby events, a novel kind of merger or explosion origin may be identified.

  11. N-Glycosylation Improves the Pepsin Resistance of Histidine Acid Phosphatase Phytases by Enhancing Their Stability at Acidic pHs and Reducing Pepsin's Accessibility to Its Cleavage Sites

    Science.gov (United States)

    Niu, Canfang; Luo, Huiying; Shi, Pengjun; Huang, Huoqing; Wang, Yaru; Yang, Peilong

    2015-01-01

    N-Glycosylation can modulate enzyme structure and function. In this study, we identified two pepsin-resistant histidine acid phosphatase (HAP) phytases from Yersinia kristensenii (YkAPPA) and Yersinia rohdei (YrAPPA), each having an N-glycosylation motif, and one pepsin-sensitive HAP phytase from Yersinia enterocolitica (YeAPPA) that lacked an N-glycosylation site. Site-directed mutagenesis was employed to construct mutants by altering the N-glycosylation status of each enzyme, and the mutant and wild-type enzymes were expressed in Pichia pastoris for biochemical characterization. Compared with those of the N-glycosylation site deletion mutants and N-deglycosylated enzymes, all N-glycosylated counterparts exhibited enhanced pepsin resistance. Introduction of the N-glycosylation site into YeAPPA as YkAPPA and YrAPPA conferred pepsin resistance, shifted the pH optimum (0.5 and 1.5 pH units downward, respectively) and improved stability at acidic pH (83.2 and 98.8% residual activities at pH 2.0 for 1 h). Replacing the pepsin cleavage sites L197 and L396 in the immediate vicinity of the N-glycosylation motifs of YkAPPA and YrAPPA with V promoted their resistance to pepsin digestion when produced in Escherichia coli but had no effect on the pepsin resistance of N-glycosylated enzymes produced in P. pastoris. Thus, N-glycosylation may improve pepsin resistance by enhancing the stability at acidic pH and reducing pepsin's accessibility to peptic cleavage sites. This study provides a strategy, namely, the manipulation of N-glycosylation, for improvement of phytase properties for use in animal feed. PMID:26637601

  12. Early GRB optical and infrared afterglow observations with the 2-m robotic Liverpool Telescope

    International Nuclear Information System (INIS)

    Gomboc, A.; Ljubljana Univ., Ljubljana; Mundell, C.G.; Guidorzi, C.

    2005-01-01

    We present the first optical observations of a Gamma Ray Burst IGRB) afterglow using the 2-m robotic Liverpool Telescope (LT), which is owned and operated by Liverpool John Moores University and situated on La Palma. We briefly discuss the capabilities of LT and its suitability for rapid follow-up observations of early optical and infrared GRB light curves. In particular, the combination of aperture, site, instrumentation and rapid response (robotic over-ride mode aided by telescope's rapid slew and fully-opening enclosure) makes the LT ideal for investigating the nature of short bursts, optically-dark bursts, and GRB blast-wave physics in general. We briefly describe the LT's key position in the RoboNet-1.0 network of robotic telescopes. We present the LT observations of GRB041006 and use its gamma-ray properties to predict the time of the break in optical light curve, a prediction consistent with the observations

  13. The LAGO Collaboration: Searching for high energy GRB emissions in Latin America

    Science.gov (United States)

    Barros, H.; Lago Collaboration

    2012-02-01

    During more than a decade Gamma Ray Bursts (GRB a cosmological phenomena of tremendous power) have been extensively studied in the keV - MeV energy range. However, the higher energy emission still remains a mystery. The Large Aperture GRB Observatory (L.A.G.O.) is an international collaboration started in 2005 aiming at a better understanding of the GRB by studying their emission at high energies (> 1 GeV), where the fluxes are low and measurements by satellites are difficult. This is done using the Single Particle Technique, by means of ground-based Water Cherenkov Detectors (WCD) at sites of high altitude. At those altitudes it is possible to detect air showers produced by high energy photons from the GRB, i. e. a higher rate of events on a short time scale, of the order of the second. The Pierre Auger Observatory could detect such GRB given its large number of detectors, but at 1400 m.a.s.l. the expected signal is quite small. At higher altitudes, similar performance is expected with only a very small number of WCD. As of 2011, high altitude WCD are in operation at Sierra Negra (Mexico, 4650 m.a.s.l.), Chacaltaya (Bolivia, 5200 m.a.s.l.), Maracapomacocha (Peru, 4200 m.a.s.l.), and new WCDs are being installed in Venezuela (Pico Espejo, 4750 m.a.s.l.), Argentina, Brazil, Chile, Colombia and Guatemala. Most of the new WCDs will not be at high enough altitude to detect GRB, never the less it will allow obtaining valuable measurements of secondaries at ground level, which are relevant for solar physics. The LAGO sensitivity to GRB is determined from simulations (under a sudden increase of 1 GeV - 1 TeV photons from a GRB) of the gamma initiated particle shower in the atmosphere and the WCD response to secondaries. We report on WDC calibration and operation at high altitude, GRB detectability, background rates, search for bursts in several months of preliminary data, as well as search for signals at ground level when satellite burst is reported, all these show the

  14. GRB 070610: A Curious Galactic Transient

    Science.gov (United States)

    Kasliwal, M. M.; Cenko, S. B.; Kulkarni, S. R.; Cameron, P. B.; Nakar, E.; Ofek, E. O.; Rau, A.; Soderberg, A. M.; Campana, S.; Bloom, J. S.; Perley, D. A.; Pollack, L. K.; Barthelmy, S.; Cummings, J.; Gehrels, N.; Krimm, H. A.; Markwardt, C. B.; Sato, G.; Chandra, P.; Frail, D.; Fox, D. B.; Price, P. A.; Berger, E.; Grebenev, S. A.; Krivonos, R. A.; Sunyaev, R. A.

    2008-05-01

    GRB 070610 is a typical high-energy event with a duration of 5 s. Yet within the burst localization we detect a highly unusual X-ray and optical transient, Swift J195509.6+261406. We see high-amplitude X-ray and optical variability on very short timescales even at late times. Using near-infrared imaging assisted by a laser guide star and adaptive optics, we identified the counterpart of Swift J195509.6+261406. Late-time optical and near-infrared imaging constrain the spectral type of the counterpart to be fainter than a K-dwarf, assuming it is of Galactic origin. It is possible that GRB 070610 and Swift J195509.6+261406 are unrelated sources. However, the absence of a typical X-ray afterglow from GRB 070610 in conjunction with the spatial and temporal coincidence of the two motivate us to suggest that the sources are related. The closest (imperfect) analog to Swift J195509.6+261406 is V4641 Sgr, an unusual black hole binary. We suggest that Swift J195509.6+261406 along with V4641 Sgr define a subclass of stellar black hole binaries—the fast X-ray novae. We further suggest that fast X-ray novae are associated with bursts of gamma rays. If so, GRB 070610 defines a new class of celestial gamma-ray bursts and these bursts dominate the long-duration GRB demographics.

  15. GRB 080913 at redshift 6.7

    DEFF Research Database (Denmark)

    Greiner, J.; Krühler, T.; Fynbo, J. P. U.

    2009-01-01

    We report on the detection by Swift of GRB 080913, and subsequent optical/near-infrared follow-up observations by GROND, which led to the discovery of its optical/NIR afterglow and the recognition of its high-z nature via the detection of a spectral break between the i' and z' bands. Spectroscopy...... obtained at the ESO-VLT revealed a continuum extending down to ¿ = 9400 Å, and zero flux for 7500 Åinterpret as the onset of a Gunn-Peterson trough at z = 6.695± 0.025 (95.5% confidence level), making GRB 080913 the highest-redshift gamma-ray burst (GRB) to date, and more distant than...

  16. GRB 110731A within the IGC paradigm

    Directory of Open Access Journals (Sweden)

    Primorac Daria

    2018-01-01

    Full Text Available Bright gamma-ray burst (GRB 110731A was simultaneously observed by Fermi and Swift observatories, with a follow up optical observation which inferred the redshift of z = 2.83. Thus, available data are spanning from optical to high energy (GeV emission. We analyze these data within the induced gravitational collapse (IGC paradigm, recently introduced to explain temporal coincidence of some long GRBs with type Ic supernovae. The case of binary-driven hypcrnova (BdHN assumes a close system, which starts as an evolved core - neutron star binary. After the core-collapse event, the new NS - black hole system is formed, emitting the GRB in the process. We performed the time-resolved and time-integrated analysis of the Fermi data. Preliminary results gave isotropic energy Eiso = 6.05 × 1053 erg and the total P-GRB energy of Ep–GRB = 3.7 × 1052 erg. At transparency point we found a Lorentz factor Γ ~ 2.17 × 103 laboratory radius of 8.33 x 1013 cm, P-GRB observed temperature of 168 keV and a baryon load B = 4.35 × 10-4. Simulated light-curve and prompt emission spectra showed the average circum burst medium density to be n ~ 0.03 particles per cm3. We reproduced the X-ray light-curve within the rest-frame of the source, finding the common late power-law behavior, with α = –1.22. Considering these results, we interpret GRB 110731A as a member of a BdHNe group.

  17. GRB 110731A within the IGC paradigm

    Science.gov (United States)

    Primorac, Daria; Ruffini, Remo; Pisani, Giovanni Battista; Aimuratov, Yerlan; Biancol, Carlo Luciano; Karlica, Mile; Melon Fuksman, Julio David; Moradi, Rahim; Muccino, Marco; Penacchioni, Ana Virginia; Rueda, Jorge Armando; Wang, Yu

    2018-01-01

    Bright gamma-ray burst (GRB) 110731A was simultaneously observed by Fermi and Swift observatories, with a follow up optical observation which inferred the redshift of z = 2.83. Thus, available data are spanning from optical to high energy (GeV) emission. We analyze these data within the induced gravitational collapse (IGC) paradigm, recently introduced to explain temporal coincidence of some long GRBs with type Ic supernovae. The case of binary-driven hypcrnova (BdHN) assumes a close system, which starts as an evolved core - neutron star binary. After the core-collapse event, the new NS - black hole system is formed, emitting the GRB in the process. We performed the time-resolved and time-integrated analysis of the Fermi data. Preliminary results gave isotropic energy Eiso = 6.05 × 1053 erg and the total P-GRB energy of Ep-GRB = 3.7 × 1052 erg. At transparency point we found a Lorentz factor Γ 2.17 × 103 laboratory radius of 8.33 x 1013 cm, P-GRB observed temperature of 168 keV and a baryon load B = 4.35 × 10-4. Simulated light-curve and prompt emission spectra showed the average circum burst medium density to be n 0.03 particles per cm3. We reproduced the X-ray light-curve within the rest-frame of the source, finding the common late power-law behavior, with α = -1.22. Considering these results, we interpret GRB 110731A as a member of a BdHNe group.

  18. Dimerization in the Grb7 Protein

    OpenAIRE

    Peterson, Tabitha A.; Benallie, Renee L.; Bradford, Andrew M.; Pias, Sally C.; Yazzie, Jaron.; Lor, Siamee N.; Haulsee, Zachary M.; Park, Chad K.; Johnson, Dennis L.; Rohrschneider, Larry R.; Spuches, Anne.; Lyons, Barbara A.

    2012-01-01

    In previous studies, we showed that the tyrosine phosphorylation state of growth factor receptor–bound protein 7 (Grb7) affects its ability to bind to the transcription regulator FHL2 and the cortactin-interacting protein, human HS-1-associated protein-1. Here, we present results describing the importance of dimerization in the Grb7–Src homology 2 (SH2) domain in terms of its structural integrity and the ability to bind phosphorylated tyrosine peptide ligands. A tyrosine phosphorylation-mimic...

  19. The GRB coordinates network (GCN): A status report

    International Nuclear Information System (INIS)

    Barthelmy, S. D.; Takeshima, T.; Butterworth, P.; Cline, T. L.; Gehrels, N.; Marshall, F.; Connaughton, V.; Kippen, R. M.; Kouveliotou, C.; Robinson, C. R.

    1998-01-01

    A review of the GRB Coordinates Network (GCN) will be given. The GCN has recently replaced the BATSE Coordinates Distribution Network (BACODINE), maintaining all of BACODINE's original capabilities and services, but also providing new sources of GRB location information. These are: (1) source locations using the MSFC LOCBURST algorithm, (2) the Rossi-XTE detections (PCA and ASM), (3) the Interplanetary Network (IPN) locations, and (4) CGRO-COMPTEL locations. These new sources of locations are available for distribution in the minutes-to-hours-to-days time delay ranges, and they also have increasingly and significantly reduced error boxes, thus providing a broad range of time delays and error box sizes to fit within the observing capabilities of a broad range of follow-up instruments in the radio, optical, and TeV gamma-ray bands. Extreme-UV transients from ALEXIS are also now distributed. For all sources of location information, all the distribution methods are available (Internet Socket, E-mail, Alpha-numeric and Numeric Pagers, and Phone/modem) and several filters. Sites can choose which sources to receive and what filters to be applied. The GCN web site has been expanded to include a globally inclusive table of locations, light-curves, and fluence information which is automatically updated in real-time

  20. H9N2 influenza virus acquires intravenous pathogenicity on the introduction of a pair of di-basic amino acid residues at the cleavage site of the hemagglutinin and consecutive passages in chickens

    Directory of Open Access Journals (Sweden)

    Sakoda Yoshihiro

    2011-02-01

    Full Text Available Abstract Background Outbreaks of avian influenza (AI caused by infection with low pathogenic H9N2 viruses have occurred in poultry, resulting in serious economic losses in Asia and the Middle East. It has been difficult to eradicate the H9N2 virus because of its low pathogenicity, frequently causing in apparent infection. It is important for the control of AI to assess whether the H9N2 virus acquires pathogenicity as H5 and H7 viruses. In the present study, we investigated whether a non-pathogenic H9N2 virus, A/chicken/Yokohama/aq-55/2001 (Y55 (H9N2, acquires pathogenicity in chickens when a pair of di-basic amino acid residues is introduced at the cleavage site of its HA molecule. Results rgY55sub (H9N2, which had four basic amino acid residues at the HA cleavage site, replicated in MDCK cells in the absence of trypsin after six consecutive passages in the air sacs of chicks, and acquired intravenous pathogenicity to chicken after four additional passages. More than 75% of chickens inoculated intravenously with the passaged virus, rgY55sub-P10 (H9N2, died, indicating that it is pathogenic comparable to that of highly pathogenic avian influenza viruses (HPAIVs defined by World Organization for Animal Health (OIE. The chickens inoculated with the virus via the intranasal route, however, survived without showing any clinical signs. On the other hand, an avirulent H5N1 strain, A/duck/Hokkaido/Vac-1/2004 (Vac1 (H5N1, acquired intranasal pathogenicity after a pair of di-basic amino acid residues was introduced into the cleavage site of the HA, followed by two passages by air sac inoculation in chicks. Conclusion The present results demonstrate that an H9N2 virus has the potential to acquire intravenous pathogenicity in chickens although the morbidity via the nasal route of infection is lower than that of H5N1 HPAIV.

  1. METALLICITY IN THE GRB 100316D/SN 2010bh HOST COMPLEX

    International Nuclear Information System (INIS)

    Levesque, Emily M.; Berger, Edo; Soderberg, Alicia M.; Chornock, Ryan

    2011-01-01

    The recent long-duration GRB 100316D, associated with supernova SN 2010bh and detected by Swift, is one of the nearest gamma-ray burst (GRB)-supernovae (SNe) ever observed (z = 0.059). This provides us with a unique opportunity to study the explosion environment on ∼kpc scale in relation to the host galaxy complex. Here we present spatially resolved spectrophotometry of the host galaxy, focusing on both the explosion site and the brightest star-forming regions. Using these data, we extract the spatial profiles of the relevant emission features (Hα, Hβ, [O III]λ5007, and [N II]λ6584) and use these profiles to examine variations in metallicity and star formation rate (SFR) as a function of position in the host galaxy. We conclude that GRB 100316D/SN2010bh occurred in a low-metallicity host galaxy, and that the GRB-SN explosion site corresponds to the region with the lowest metallicity and highest SFR sampled by our observations.

  2. Short GRB afterglows observed with GROND

    DEFF Research Database (Denmark)

    Nicuesa Guelbenzu, A.; Klose, S.; Rossi, A.

    2013-01-01

    We report on follow-up observations of 20 short-duration gamma-ray bursts (T90 < 2s) performed in g′r′i′z′JHK s with the Gamma-Ray Burst Optical Near-Infrared Detector (GROND) between mid-2007 and the end of 2010. This is the most homogeneous and comprehensive data set on GRB afterglow observatio...

  3. Mapping DNA cleavage by the Type ISP restriction-modification enzymes following long-range communication between DNA sites in different orientations

    OpenAIRE

    van Aelst, Kara; Saikrishnan, Kayarat; Szczelkun, Mark D

    2015-01-01

    The prokaryotic Type ISP restriction-modification enzymes are single-chain proteins comprising an Mrr-family nuclease, a superfamily 2 helicase-like ATPase, a coupler domain, a methyltransferase, and a DNA-recognition domain. Upon recognising an unmodified DNA target site, the helicase-like domain hydrolyzes ATP to cause site release (remodeling activity) and to then drive downstream translocation consuming 1-2 ATP per base pair (motor activity). On an invading foreign DNA, double-strand brea...

  4. HOST GALAXY PROPERTIES OF THE SUBLUMINOUS GRB 120422A/SN 2012bz

    Energy Technology Data Exchange (ETDEWEB)

    Levesque, Emily M. [CASA, Department of Astrophysical and Planetary Sciences, University of Colorado 389-UCB, Boulder, CO 80309 (United States); Chornock, Ryan; Soderberg, Alicia M.; Berger, Edo; Lunnan, Ragnhild, E-mail: Emily.Levesque@colorado.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

    2012-10-20

    GRB 120422A is a nearby (z = 0.283) long-duration gamma-ray burst (LGRB) detected by Swift with E {sub {gamma},iso} {approx} 4.5 Multiplication-Sign 10{sup 49} erg. It is also associated with the spectroscopically confirmed broad-lined Type Ic SN 2012bz. These properties establish GRB 120422A/SN 2012bz as the sixth and newest member of the class of subluminous GRBs supernovae (SNe). Observations also show that GRB 120422A/SN 2012bz occurred at an unusually large offset ({approx}8 kpc) from the host galaxy nucleus, setting it apart from other nearby LGRBs and leading to speculation that the host environment may have undergone prior interaction activity. Here, we present spectroscopic observations using the 6.5 m Magellan telescope at Las Campanas. We extract spectra at three specific locations within the GRB/SN host galaxy, including the host nucleus, the explosion site, and the 'bridge' of diffuse emission connecting these two regions. We measure a metallicity of log(O/H) + 12 = 8.3 {+-} 0.1 and a star formation rate (SFR) per unit area of 0.08 M {sub Sun} yr{sup -1} kpc{sup -2} at the host nucleus. At the GRB/SN explosion site we measure a comparable metallicity of log(O/H) + 12 = 8.2 {+-} 0.1 but find a much lower SFR per unit area of 0.01 M {sub Sun} yr{sup -1} kpc{sup -2}. We also compare the host galaxy of this event to the hosts of other LGRBs, including samples of subluminous LGRBs and cosmological LGRBs, and find no systematic metallicity difference between the environments of these different subtypes.

  5. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase.

    Science.gov (United States)

    Schlaepfer, D D; Hanks, S K; Hunter, T; van der Geer, P

    The cytoplasmic focal adhesion protein-tyrosine kinase (FAK) localizes with surface integrin receptors at sites where cells attach to the extracellular matrix. Increased FAK tyrosine phosphorylation occurs upon integrin engagement with fibronectin. Here we show that adhesion of murine NIH3T3 fibroblasts to fibronectin promotes SH2-domain-mediated association of the GRB2 adaptor protein and the c-Src protein-tyrosine kinase (PTK) with FAK in vivo, and also results in activation of mitogen-activated protein kinase (MAPK). In v-Src-transformed NIH3T3, the association of v-Src, GRB2 and Sos with FAK is independent of cell adhesion to fibronectin. The GRB2 SH2 domain binds directly to tyrosine-phosphorylated FAK. Mutation of tyrosine residue 925 of FAK (YENV motif) to phenylalanine blocks GRB2 SH2-domain binding to FAK in vitro. Our results show that fibronectin binding to integrins on NIH3T3 fibroblasts promotes c-Src and FAK association and formation of an integrin-activated signalling complex. Phosphorylation of FAK at Tyr 925 upon fibronectin stimulation creates an SH2-binding site for GRB2 which may link integrin engagement to the activation of the Ras/MAPK signal transduction pathway.

  6. Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins

    DEFF Research Database (Denmark)

    Salcini, A E; McGlade, J; Pelicci, G

    1994-01-01

    The mammalian SHC gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are phosphorylated on tyrosine by a variety of receptor and cytoplasmic tyrosine kinases. Phosphorylated Shc proteins form a complex with the SH2-SH3 containing Grb2 protein which...... of Grb2 to Shc proteins requires phosphorylation of Shc at Tyr317, which lies within the high affinity binding motif for the Grb2 SH2 domain, pYVNV, where Asn at the +2 position is crucial for complex formation. In vivo, Tyr317 is the major, but not the only, site for Shc phosphorylation, and is the sole...... aminoterminal deletion, but retain the Tyr317 site and the SH2 domain conserve the capacity to be phosphorylated, to bind to Grb2 and to induce cell transformation. These data indicate that the formation of the Shc-Grb2 complex is a crucial event in the transformation induced by overexpression of Shc...

  7. Gas Kinematics in GRB Host Galaxies

    DEFF Research Database (Denmark)

    Arabsalmani, Maryam

    towards a relation between gas kinematics and mass. This also provides information on how the metallicities measured from absorption and emission methods differ from each other. Finally, in a direct study I show that gas velocity widths in both phases can be used as a proxy of stellar mass...... that their interstellar media imprint on the GRBs’ spectra. Hence they are invaluable tools to probe the star formation history of the Universe back to the earliest cosmic epochs. To this end, it is essential to achieve a comprehensive picture of the interplay between star formation and its fuel, neutral gas, in GRB...... simultaneously with a high velocity resolution. For the large GRB sample, I find the spatially averaged velocity to correlate with metallicity in both gas phases. This is an indicator of a mass-metallicity relation. Moreover, the velocity widths in the two gas phases correlate with each other which too points...

  8. Possible GRB Observation with the MAGIC Telescope

    Science.gov (United States)

    Bastieri, D.; Bigongiari, C.; Mariotti, M.; Peruzzo, L.; Saggion, A.

    2001-08-01

    The MAGIC Telescope, with its reflecting parabolic dish of 17 m of diameter and its careful design of a robust, lightweight, alto-azimuthal mount, is an ideal detector for GRB phenomena. The telescope is an air Cherenkov telescope that, even in the first phase, equipped with standard PMTs, can reach an energy threshold below 30 GeV. The threshold is going to drop well below 10 GeV in the envisaged second phase, when chamber PMTs will be substituted by high quantum efficiency APDs. The telescope can promptly respond to GRB alerts coming, for instance, from GCN, and can reposition itself in less than 30 seconds, 20 seconds being the time to turn half a round for the azimuth bearing. In this report, the effective area of the detector as a function of energy and zenith angle is taken into account, in order to evaluate the expected yearly occurrence and the response to different kinds of GRBs.

  9. Spectroscopy of the short-hard GRB 130603B

    DEFF Research Database (Denmark)

    Postigo, A. de Ugarte; Thoene, C. C.; Rowlinson, A.

    2014-01-01

    with the Galactic ratio, indicating that the explosion site differs from those found in LGRBs. The merger is not associated with the most star-forming region of the galaxy; however, it did occur in a dense region, implying a rapid merger or a low natal kick velocity for the compact object binary........3565+/-0.0002, measure rich dynamics both in absorption and emission, and a substantial line of sight extinction of A_V = 0.86+/-0.15 mag. The GRB was located at the edge of a disrupted arm of a moderately star forming galaxy with near-solar metallicity. Unlike for most long GRBs (LGRBs), N_HX / A_V is consistent...

  10. Use of water-Cherenkov detectors to detect Gamma Ray Bursts at the Large Aperture GRB Observatory (LAGO)

    International Nuclear Information System (INIS)

    Allard, D.; Allekotte, I.; Alvarez, C.; Asorey, H.; Barros, H.; Bertou, X.; Burgoa, O.; Gomez Berisso, M.; Martinez, O.; Miranda Loza, P.; Murrieta, T.; Perez, G.; Rivera, H.; Rovero, A.; Saavedra, O.; Salazar, H.; Tello, J.C.; Ticona Peralda, R.; Velarde, A.; Villasenor, L.

    2008-01-01

    The Large Aperture GRB Observatory (LAGO) project aims at the detection of high energy photons from Gamma Ray Bursts (GRB) using the single particle technique in ground-based water-Cherenkov detectors (WCD). To reach a reasonable sensitivity, high altitude mountain sites have been selected in Mexico (Sierra Negra, 4550 m a.s.l.), Bolivia (Chacaltaya, 5300 m a.s.l.) and Venezuela (Merida, 4765 m a.s.l.). We report on detector calibration and operation at high altitude, search for bursts in 4 months of preliminary data, as well as search for signal at ground level when satellites report a burst

  11. Use of water-Cherenkov detectors to detect Gamma Ray Bursts at the Large Aperture GRB Observatory (LAGO)

    Energy Technology Data Exchange (ETDEWEB)

    Allard, D. [APC, CNRS et Universite Paris 7 (France); Allekotte, I. [Centro Atomico Bariloche, Instituto Balseiro (Argentina); Alvarez, C. [Facultad de Ciencias Fisico-Matematicas de la BUAP (Mexico); Asorey, H. [Centro Atomico Bariloche, Instituto Balseiro (Argentina); Barros, H. [Laboratorio de Fisica Nuclear, Universidad Simon Bolivar, Caracas (Venezuela, Bolivarian Republic of); Bertou, X. [Centro Atomico Bariloche, Instituto Balseiro (Argentina)], E-mail: bertou@cab.cnea.gov.ar; Burgoa, O. [Instituto de Investigaciones Fisicas, UMSA (Bolivia); Gomez Berisso, M. [Centro Atomico Bariloche, Instituto Balseiro (Argentina); Martinez, O. [Facultad de Ciencias Fisico-Matematicas de la BUAP (Mexico); Miranda Loza, P. [Instituto de Investigaciones Fisicas, UMSA (Bolivia); Murrieta, T.; Perez, G. [Facultad de Ciencias Fisico-Matematicas de la BUAP (Mexico); Rivera, H. [Instituto de Investigaciones Fisicas, UMSA (Bolivia); Rovero, A. [Instituto de Astronomia y Fisica del Espacio (Argentina); Saavedra, O. [Dipartimento di Fisica Generale and INFN, Torino (Italy); Salazar, H. [Facultad de Ciencias Fisico-Matematicas de la BUAP (Mexico); Tello, J.C. [Laboratorio de Fisica Nuclear, Universidad Simon Bolivar, Caracas (Venezuela, Bolivarian Republic of); Ticona Peralda, R.; Velarde, A. [Instituto de Investigaciones Fisicas, UMSA (Bolivia); Villasenor, L. [Facultad de Ciencias Fisico-Matematicas de la BUAP (Mexico); Instituto de Fisica y Matematicas, Universidad de Michoacan (Mexico)

    2008-09-21

    The Large Aperture GRB Observatory (LAGO) project aims at the detection of high energy photons from Gamma Ray Bursts (GRB) using the single particle technique in ground-based water-Cherenkov detectors (WCD). To reach a reasonable sensitivity, high altitude mountain sites have been selected in Mexico (Sierra Negra, 4550 m a.s.l.), Bolivia (Chacaltaya, 5300 m a.s.l.) and Venezuela (Merida, 4765 m a.s.l.). We report on detector calibration and operation at high altitude, search for bursts in 4 months of preliminary data, as well as search for signal at ground level when satellites report a burst.

  12. Capturing the Alternative Cleavage and Polyadenylation Sites of 14 NAC Genes in Populus Using a Combination of 3′-RACE and High-Throughput Sequencing

    Directory of Open Access Journals (Sweden)

    Haoran Wang

    2018-03-01

    Full Text Available Detection of complex splice sites (SSs and polyadenylation sites (PASs of eukaryotic genes is essential for the elucidation of gene regulatory mechanisms. Transcriptome-wide studies using high-throughput sequencing (HTS have revealed prevalent alternative splicing (AS and alternative polyadenylation (APA in plants. However, small-scale and high-depth HTS aimed at detecting genes or gene families are very few and limited. We explored a convenient and flexible method for profiling SSs and PASs, which combines rapid amplification of 3′-cDNA ends (3′-RACE and HTS. Fourteen NAC (NAM, ATAF1/2, CUC2 transcription factor genes of Populus trichocarpa were analyzed by 3′-RACE-seq. Based on experimental reproducibility, boundary sequence analysis and reverse transcription PCR (RT-PCR verification, only canonical SSs were considered to be authentic. Based on stringent criteria, candidate PASs without any internal priming features were chosen as authentic PASs and assumed to be PAS-rich markers. Thirty-four novel canonical SSs, six intronic/internal exons and thirty 3′-UTR PAS-rich markers were revealed by 3′-RACE-seq. Using 3′-RACE and real-time PCR, we confirmed that three APA transcripts ending in/around PAS-rich markers were differentially regulated in response to plant hormones. Our results indicate that 3′-RACE-seq is a robust and cost-effective method to discover SSs and label active regions subjected to APA for genes or gene families. The method is suitable for small-scale AS and APA research in the initial stage.

  13. Photoaffinity labeling of human serum vitamin D binding protein and chemical cleavage of the labeled protein: Identification of an 11.5-kDa peptide containing the putative 25-hydroxyvitamin D3 binding site

    International Nuclear Information System (INIS)

    Ray, R.; Holick, M.F.; Bouillon, R.; Baelen, H.V.

    1991-01-01

    In this paper, the authors describe photoaffinity labeling and related studies of human serum vitamin D binding protein (hDBP) with 25-hydroxyvitamin D 3 3β-3'-[N-(4-azido-2-nitrophenyl)amino]propyl ether (25-ANE) and its radiolabeled counterpart, i.e., 25-hydroxyvitamin D 3 3β-3'-[N-(4-azido-2-nitro-[3,5- 3 H]phenyl)amino]propyl ether ( 3 H-25-ANE). They have carried out studies to demonstrate that (1) 25-ANE competes with 25-OH-D 3 for the binding site of the latter in hDBP and (2) 3 H-25-ANE is capable of covalently labeling the hDBP molecule when exposed ot UV light. Treatment of a sample of purified hDBP, labeled with 3 H-25-ANE, with BNPS-skatole produced two Coomassie Blue stained peptide fragments, and the majority of the radioactivity was assoicated with the smaller of the two peptide fragments (16.5 kDa). On the other hand, cleavage of the labeled protein with cyanogen bromide produced a peptide (11.5 kDa) containing most of the covalently attached radioactivity. Considering the primary amino acid structure of hDBP, this peptide fragment (11.5 kDa) represents the N-terminus through residue 108 of the intact protein. Thus, the results tentatively identify this segment of the protein containing the binding pocket for 25-OH-D 3

  14. GRB 030329: 3 years of radio afterglow monitoring

    NARCIS (Netherlands)

    van der Horst, A.J.; Kamble, A.; Wijers, R.A.M.J.; Resmi, L.; Bhattacharya, D.; Rol, E.; Strom, R.; Kouveliotou, C.; Oosterloo, T.; Ishwara-Chandra, C.H.

    2007-01-01

    Radio observations of gamma-ray burst (GRB) afterglows are essential for our understanding of the physics of relativistic blast waves, as they enable us to follow the evolution of GRB explosions much longer than the afterglows in any other wave band. We have performed a three-year monitoring

  15. Detection of nucleic acid sequences by invader-directed cleavage

    Science.gov (United States)

    Brow, Mary Ann D.; Hall, Jeff Steven Grotelueschen; Lyamichev, Victor; Olive, David Michael; Prudent, James Robert

    1999-01-01

    The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The 5' nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof. The present invention further relates to methods and devices for the separation of nucleic acid molecules based by charge.

  16. The sub-energetic gamma-ray burst GRB 031203 as a cosmic analogue to the nearby GRB 980425.

    Science.gov (United States)

    Soderberg, A M; Kulkarni, S R; Berger, E; Fox, D W; Sako, M; Frail, D A; Gal-Yam, A; Moon, D S; Cenko, S B; Yost, S A; Phillips, M M; Persson, S E; Freedman, W L; Wyatt, P; Jayawardhana, R; Paulson, D

    2004-08-05

    Over the six years since the discovery of the gamma-ray burst GRB 980425, which was associated with the nearby (distance approximately 40 Mpc) supernova 1998bw, astronomers have debated fiercely the nature of this event. Relative to bursts located at cosmological distance (redshift z approximately 1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed that the explosion was sub-energetic by a factor of 10. Here we report observations of the radio and X-ray afterglow of the recent GRB 031203 (refs 5-7), which has a redshift of z = 0.105. We demonstrate that it too is sub-energetic which, when taken together with the low gamma-ray luminosity, suggests that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. We expect intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRB 031203 and 980425) to reveal a large population of such events.

  17. The Structure and Dynamics of GRB Jets

    Energy Technology Data Exchange (ETDEWEB)

    Granot, Jonathan; /KIPAC, Menlo Park

    2006-10-25

    There are several lines of evidence which suggest that the relativistic outflows in gamma-ray bursts (GRBs) are collimated into narrow jets. The jet structure has important implications for the true energy release and the event rate of GRBs, and can constrain the mechanism responsible for the acceleration and collimation of the jet. Nevertheless, the jet structure and its dynamics as it sweeps up the external medium and decelerates, are not well understood. In this review I discuss our current understanding of GRB jets, stressing their structure and dynamics.

  18. GRB 070610: a curious galactic transient

    OpenAIRE

    Kasliwal, M. M.; Cenko, S. B.; Kulkarni, S. R.; Cameron, P. B.; Nakar, E.; Ofek, E. O.; Rau, A.; Soderberg, A. M.; Campana, S.; Bloom, J. S.; Perley, D. A.; Pollack, L. K.; Barthelmy, S.; Cummings, J.; Gehrels, N.

    2008-01-01

    GRB 070610 is a typical high-energy event with a duration of 5 s. Yet within the burst localization we detect a highly unusual X-ray and optical transient, Swift J195509.6+261406. We see high-amplitude X-ray and optical variability on very short timescales even at late times. Using near-infrared imaging assisted by a laser guide star and adaptive optics, we identified the counterpart of Swift J195509.6+261406. Late-time optical and near-infrared imaging constrain the spectral type of the coun...

  19. Intermolecular cleavage by UmuD-like mutagenesis proteins

    Science.gov (United States)

    McDonald, John P.; Frank, Ekaterina G.; Levine, Arthur S.; Woodgate, Roger

    1998-01-01

    The activity of a number of proteins is regulated by self-processing reactions. Elegant examples are the cleavage of the prokaryotic LexA and λCI transcriptional repressors and the UmuD-like mutagenesis proteins. Various studies support the hypothesis that LexA and λCI cleavage reactions are predominantly intramolecular in nature. The recently described crystal structure of the Escherichia coli UmuD′ protein (the posttranslational cleavage product of the UmuD protein) suggests, however, that the region of the protein corresponding to the cleavage site is at least 50 Å away from the catalytic active site. We considered the possibility, therefore, that the UmuD-like proteins might undergo self-processing that, in contrast to LexA and λCI, occurs via an intermolecular rather than intramolecular reaction. To test this hypothesis, we introduced into E. coli compatible plasmids with mutations at either the cleavage or the catalytic site of three UmuD-like proteins. Cleavage of these proteins only occurs in the presence of both plasmids, indicating that the reaction is indeed intermolecular in nature. Furthermore, this intermolecular reaction is completely dependent upon the multifunctional RecA protein and leads to the restoration of cellular mutagenesis in nonmutable E. coli strains. Intermolecular cleavage of a biotinylated UmuD active site mutant was also observed in vitro in the presence of the wild-type UmuD′ protein, indicating that in addition to the intact UmuD protein, the normal cleavage product (UmuD′) can also act as a classical enzyme. PMID:9465040

  20. Prediction of proprotein convertase cleavage sites

    DEFF Research Database (Denmark)

    Duckert, Peter; Brunak, Søren; Blom, Nikolaj

    2004-01-01

    by members of the subtilisin/kexin-like proprotein convertase (PC) family. In mammals, seven members have been identified, with furin being the one first discovered and best characterized. Recently, the involvement of furin in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever...

  1. A binary neutron star GRB model

    International Nuclear Information System (INIS)

    Wilson, J.R.; Salmonson, J.D.; Wilson, J.R.; Mathews, G.J.

    1998-01-01

    In this paper we present the preliminary results of a model for the production of gamma-ray bursts (GRBs) through the compressional heating of binary neutron stars near their last stable orbit prior to merger. Recent numerical studies of the general relativistic (GR) hydrodynamics in three spatial dimensions of close neutron star binaries (NSBs) have uncovered evidence for the compression and heating of the individual neutron stars (NSs) prior to merger 12. This effect will have significant effect on the production of gravitational waves, neutrinos and, ultimately, energetic photons. The study of the production of these photons in close NSBs and, in particular, its correspondence to observed GRBs is the subject of this paper. The gamma-rays arise as follows. Compressional heating causes the neutron stars to emit neutrino pairs which, in turn, annihilate to produce a hot electron-positron pair plasma. This pair-photon plasma expands rapidly until it becomes optically thin, at which point the photons are released. We show that this process can indeed satisfy three basic requirements of a model for cosmological gamma-ray bursts: (1) sufficient gamma-ray energy release (>10 51 ergs) to produce observed fluxes, (2) a time-scale of the primary burst duration consistent with that of a 'classical' GRB (∼10 seconds), and (3) the peak of the photon number spectrum matches that of 'classical' GRB (∼300 keV). copyright 1998 American Institute of Physics

  2. The host galaxy of GRB 990712

    DEFF Research Database (Denmark)

    Christensen, L.; Hjorth, J.; Gorosabel, J.

    2004-01-01

    We present a comprehensive study of the z = 0.43 host galaxy of GRB 990712, involving ground-based photometry, spectroscopy, and HST imaging. The broad-band UBVRIJHKs photometry is used to determine the global spectral energy distribution (SED) of the host galaxy. Comparison with that of known...... galaxy types shows that the host is similar to a moderately kreddened starburst galaxy with a young stellar population. The estimated internal extinction in the host is A(V) = 0.15 +/- 0.1 and the star-formation rate (SFR) from the UV continuum is 1.3 +/- 0.3 M-circle dot yr(-1) (not corrected...... for the effects of extinction). Other galaxy template spectra than starbursts failed to reproduce the observed SED. We also present VLT spectra leading to the detection of Halpha from the GRB host galaxy. A SFR of 2.8 +/- 0.7 M-circle dot yr(-1) is inferred from the Halpha line flux, and the presence of a young...

  3. Vertebrate Embryonic Cleavage Pattern Determination.

    Science.gov (United States)

    Hasley, Andrew; Chavez, Shawn; Danilchik, Michael; Wühr, Martin; Pelegri, Francisco

    2017-01-01

    The pattern of the earliest cell divisions in a vertebrate embryo lays the groundwork for later developmental events such as gastrulation, organogenesis, and overall body plan establishment. Understanding these early cleavage patterns and the mechanisms that create them is thus crucial for the study of vertebrate development. This chapter describes the early cleavage stages for species representing ray-finned fish, amphibians, birds, reptiles, mammals, and proto-vertebrate ascidians and summarizes current understanding of the mechanisms that govern these patterns. The nearly universal influence of cell shape on orientation and positioning of spindles and cleavage furrows and the mechanisms that mediate this influence are discussed. We discuss in particular models of aster and spindle centering and orientation in large embryonic blastomeres that rely on asymmetric internal pulling forces generated by the cleavage furrow for the previous cell cycle. Also explored are mechanisms that integrate cell division given the limited supply of cellular building blocks in the egg and several-fold changes of cell size during early development, as well as cytoskeletal specializations specific to early blastomeres including processes leading to blastomere cohesion. Finally, we discuss evolutionary conclusions beginning to emerge from the contemporary analysis of the phylogenetic distributions of cleavage patterns. In sum, this chapter seeks to summarize our current understanding of vertebrate early embryonic cleavage patterns and their control and evolution.

  4. Grb2 mediates semaphorin-4D-dependent RhoA inactivation.

    Science.gov (United States)

    Sun, Tianliang; Krishnan, Rameshkumar; Swiercz, Jakub M

    2012-08-01

    Signaling through the semaphorin 4D (Sema4D) receptor plexin-B1 is modulated by its interaction with tyrosine kinases ErbB-2 and Met. In cells expressing the plexin-B1-ErbB-2 receptor complex, ligand stimulation results in the activation of small GTPase RhoA and stimulation of cellular migration. By contrast, in cells expressing plexin-B1 and Met, ligand stimulation results in an association with the RhoGTPase-activating protein p190 RhoGAP and subsequent RhoA inactivation--a process that involves the tyrosine phosphorylation of plexin-B1 by Met. Inactivation of RhoA is necessary for Sema4D-mediated inhibition of cellular migration. It is, however, unknown how plexin-B1 phosphorylation regulates RhoGAP interaction and activity. Here we show that the activation of plexin-B1 by Sema4D and its subsequent tyrosine phosphorylation by Met creates a docking site for the SH2 domain of growth factor receptor bound-2 (Grb2). Grb2 is thereby recruited into the plexin-B1 receptor complex and, through its SH3 domain, interacts with p190 RhoGAP and mediates RhoA deactivation. Phosphorylation of plexin-B1 by Met and the recruitment of Grb2 have no effect on the R-RasGAP activity of plexin-B1, but are required for Sema4D-induced, RhoA-dependent antimigratory effects of Sema4D on breast cancer cells. These data show Grb2 as a direct link between plexin and p190-RhoGAP-mediated downstream signaling.

  5. Sequence specific inhibition of DNA restriction enzyme cleavage by PNA

    DEFF Research Database (Denmark)

    Nielsen, P.E.; Egholm, M.; Berg, R.H.

    1993-01-01

    Plasmids containing double-stranded 10-mer PNA (peptide nucleic acid chimera) targets proximally flanked by two restriction enzyme sites were challenged with the complementary PNA or PNAs having one or two mismatches, and the effect on the restriction enzyme cleavage of the flanking sites was ass...

  6. Fermi Observation of GRB 080916C

    International Nuclear Information System (INIS)

    Piron, F.

    2009-01-01

    We present the observations of the long-duration Gamma-Ray Burst GRB 080916C by the Fermi Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT). This event was observed from 8 keV to a photon with an energy of 13.2 GeV. It develops over a 1400 s interval during which the highest number of photons with energy above 100 MeV are detected from a burst. The onset of the high-energy (>100 MeV) emission is delayed by ∼4.5 s with respect to the low-energy (<1 MeV) emission, which is not detected past 200 s. The broad-band spectrum of the burst is consistent with a single spectral form.

  7. The Accuracy of GBM GRB Localizations

    Science.gov (United States)

    Briggs, Michael Stephen; Connaughton, V.; Meegan, C.; Hurley, K.

    2010-03-01

    We report an study of the accuracy of GBM GRB localizations, analyzing three types of localizations: those produced automatically by the GBM Flight Software on board GBM, those produced automatically with ground software in near real time, and localizations produced with human guidance. The two types of automatic locations are distributed in near real-time via GCN Notices; the human-guided locations are distributed on timescale of many minutes or hours using GCN Circulars. This work uses a Bayesian analysis that models the distribution of the GBM total location error by comparing GBM locations to more accurate locations obtained with other instruments. Reference locations are obtained from Swift, Super-AGILE, the LAT, and with the IPN. We model the GBM total location errors as having systematic errors in addition to the statistical errors and use the Bayesian analysis to constrain the systematic errors.

  8. a new approach of Analysing GRB light curves

    International Nuclear Information System (INIS)

    Varga, B.; Horvath, I.

    2005-01-01

    We estimated the T xx quantiles of the cumulative GRB light curves using our recalculated background. The basic information of the light curves was extracted by multivariate statistical methods. The possible classes of the light curves are also briefly discussed

  9. High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.

    Directory of Open Access Journals (Sweden)

    Kunitake Higo

    Full Text Available Src homology 2 (SH2 domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2 specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

  10. High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.

    Science.gov (United States)

    Higo, Kunitake; Ikura, Teikichi; Oda, Masayuki; Morii, Hisayuki; Takahashi, Jun; Abe, Ryo; Ito, Nobutoshi

    2013-01-01

    Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

  11. CONSTRAINTS ON VERY HIGH ENERGY EMISSION FROM GRB 130427A

    International Nuclear Information System (INIS)

    Aliu, E.; Errando, M.; Aune, T.; Barnacka, A.; Beilicke, M.; Buckley, J. H.; Bugaev, V.; Benbow, W.; Cerruti, M.; Berger, K.; Biteau, J.; Byrum, K.; Cardenzana, J. V; Dickinson, H. J.; Eisch, J. D.; Chen, X.; Ciupik, L.; Connaughton, V.; Cui, W.; Falcone, A.

    2014-01-01

    Prompt emission from the very fluent and nearby (z = 0.34) gamma-ray burst GRB 130427A was detected by several orbiting telescopes and by ground-based, wide-field-of-view optical transient monitors. Apart from the intensity and proximity of this GRB, it is exceptional due to the extremely long-lived high-energy (100 MeV to 100 GeV) gamma-ray emission, which was detected by the Large Area Telescope on the Fermi Gamma-Ray Space Telescope for ∼70 ks after the initial burst. The persistent, hard-spectrum, high-energy emission suggests that the highest-energy gamma rays may have been produced via synchrotron self-Compton processes though there is also evidence that the high-energy emission may instead be an extension of the synchrotron spectrum. VERITAS, a ground-based imaging atmospheric Cherenkov telescope array, began follow-up observations of GRB 130427A ∼71 ks (∼20 hr) after the onset of the burst. The GRB was not detected with VERITAS; however, the high elevation of the observations, coupled with the low redshift of the GRB, make VERITAS a very sensitive probe of the emission from GRB 130427A for E > 100 GeV. The non-detection and consequent upper limit derived place constraints on the synchrotron self-Compton model of high-energy gamma-ray emission from this burst

  12. Prediction of proteasome cleavage motifs by neural networks

    DEFF Research Database (Denmark)

    Kesimir, C.; Nussbaum, A.K.; Schild, H.

    2002-01-01

    physiological conditions. Our algorithm has been trained not only on in vitro data, but also on MHC Class I ligand data, which reflect a combination of immunoproteasome and constitutive proteasome specificity. This feature, together with the use of neural networks, a non-linear classification technique, make...... the prediction of MHC Class I ligand boundaries more accurate: 65% of the cleavage sites and 85% of the non-cleavage sites are correctly determined. Moreover, we show that the neural networks trained on the constitutive proteasome data learns a specificity that differs from that of the networks trained on MHC...

  13. Two Early Gamma-ray Bursts Optical Afterglow Detections with TAOS Telescopes--GRB 071010B and GRB 071112C

    International Nuclear Information System (INIS)

    Huang, K. Y.; Wang, S. Y.; Urata, Y.

    2009-01-01

    We present on two early detections of GRB afterglows with the Taiwanese-American Occltation Sruvey (TAOS) telescopes. The robotic TAOS system has been devised so that the routine Kuiper Belt Object (KBO) survey is interrupted when a GRB alert is triggered. Our first detection, GRB 071010B was detected by TAOS 62 s after the burst and showed a weak early brightening during the observations. No significant correction with the prompt gamma-ray emission indicated that our optical emission detected is afterglow emission. The second detection of TAOS, GRB 071112C was detected 96 s after the burst, also showed a possible initial raising then followed a steep decay in the R-band light curve.

  14. Molecular cloning of the mouse grb2 gene: differential interaction of the Grb2 adaptor protein with epidermal growth factor and nerve growth factor receptors.

    OpenAIRE

    Suen, K L; Bustelo, X R; Pawson, T; Barbacid, M

    1993-01-01

    We report the isolation and molecular characterization of the mouse grb2 gene. The product of this gene, the Grb2 protein, is highly related to the Caenorhabditis elegans sem-5 gene product and the human GRB2 protein and displays the same SH3-SH2-SH3 structural motifs. In situ hybridization studies revealed that the mouse grb2 gene is widely expressed throughout embryonic development (E9.5 to P0). However, grb2 transcripts are not uniformly distributed, and in certain tissues (e.g., thymus) t...

  15. The GW170817/GRB 170817A/AT 2017gfo Association: Some Implications for Physics and Astrophysics

    Science.gov (United States)

    Wang, Hao; Zhang, Fu-Wen; Wang, Yuan-Zhu; Shen, Zhao-Qiang; Liang, Yun-Feng; Li, Xiang; Liao, Neng-Hui; Jin, Zhi-Ping; Yuan, Qiang; Zou, Yuan-Chuan; Fan, Yi-Zhong; Wei, Da-Ming

    2017-12-01

    On 2017 August 17, a gravitational-wave event (GW170817) and an associated short gamma-ray burst (GRB 170817A) from a binary neutron star merger had been detected. The follow-up optical/infrared observations also identified the macronova/kilonova emission (AT 2017gfo). In this work, we discuss some implications of the remarkable GW170817/GRB 170817A/AT 2017gfo association. We show that the ∼1.7 s time delay between the gravitational-wave (GW) and GRB signals imposes very tight constraints on the superluminal movement of gravitational waves (i.e., the relative departure of GW velocity from the speed of light is ≤slant 4.3× {10}-16) or the possible violation of the weak equivalence principle (i.e., the difference of the gamma-ray and GW trajectories in the gravitational field of the galaxy and the local universe should be within a factor of ∼ 3.4× {10}-9). The so-called Dark Matter Emulators and a class of contender models for cosmic acceleration (“Covariant Galileon”) are ruled out as well. The successful identification of lanthanide elements in the macronova/kilonova spectrum also excludes the possibility that the progenitors of GRB 170817A are a binary strange star system. The high neutron star merger rate (inferred from both the local sGRB data and the gravitational-wave data) together with the significant ejected mass strongly suggest that such mergers are the prime sites of heavy r-process nucleosynthesis.

  16. A Fe K Line in GRB 970508

    Science.gov (United States)

    Protassov, R.; van Dyk, D.; Connors, A.; Kashyap, V.; Siemiginowska, A.

    2000-12-01

    We examine the x-ray spectrum of the afterglow of GRB 970508, analyzed for Fe line emission by Piro et al (1999, ApJL, 514, L73). This is a difficult and extremely important measurement: the detection of x-ray afterglows from γ -ray bursts is at best a tricky business, relying on near-real satellite time response to unpredictable events; and a great deal of luck in catching a burst bright enough for a useful spectral analysis. Detecting a clear atomic (or cyclotron) line in the generally smooth and featureless afterglow (or burst) emission not only gives one of the few very specific keys to the physics local to the emission region, but also provides clues or confirmation of its distance (via redshift). Unfortunately, neither the likelihood ratio test or the related F-statistic commonly used to detect spectral lines adhere to their nominal Chi square and F-distributions. Thus we begin by calibrating the F-statistic used in Piro et al (1999, ApJL, 514, L73) via a simulation study. The simulation study relies on a completely specified source model, i.e. we do Monte Carlo simulations with all model parameters fixed (so--called ``parametric bootstrapping''). Second, we employ the method of posterior predictive p-values to calibrate a LRT statistic while accounting for the uncertainty in the parameters of the source model. Our analysis reveals evidence for the Fe K line.

  17. Hyper-Eddington accretion in GRB

    International Nuclear Information System (INIS)

    Janiuk, A.; Czerny, B.; Perna, R.; Di Matteo, T.

    2005-01-01

    Popular models of the GRB origin associate this event with a cosmic explosion, birth of a stellar mass black ho le and jet ejection. Due to the shock collisions that happen in the jet, the gamma rays are produced and we detect a burst of duration up to several tens of seconds. This burst duration is determined by the lifetime of the central engine, which may be different in various scenarios. Characteristically, the observed bursts have a bimodal distribution and constitute the two classes: short (t < 2 s) and long bursts. Theoretical models invoke the mergers of two neutron stars or a neutron star with a black hole, or, on the other hand, a massive star explosion (collapsar). In any of these models we have a phase of disc accretion onto a newly born black hole: the di se is formed from the disrupted neutron star or fed by the material fallback from the ejected collapsar envelope. The disc is extremely hot and dense, and the accretion rate is orders of magnitude higher than the Eddington rate. In such physical conditions the main cooling mechanism is neutrino emission, and one of possible ways of energy extraction from the accretion disc is the neutrino-antineutrino annihilation

  18. Growth of chronic myeloid leukemia cells is inhibited by infection with Ad-SH2-HA adenovirus that disrupts Grb2-Bcr-Abl complexes.

    Science.gov (United States)

    Peng, Zhi; Luo, Hong-Wei; Yuan, Ying; Shi, Jing; Huang, Shi-Feng; Li, Chun-Li; Cao, Wei-Xi; Huang, Zong-Gan; Feng, Wen-Li

    2011-05-01

    The persistence of Bcr-Abl-positive cells in patients on imatinib therapy indicates that inhibition of the Bcr-Abl kinase activity alone might not be sufficient to eradicate the leukemia cells. Many downstream effectors of Bcr-Abl have been described, including activation of both the Grb2-SoS-Ras-MAPK and Grb2-Gab2-PI3K-Akt pathways. The Bcr-Abl-Grb2 interaction, which is mediated by the direct interaction of the Grb2 SH2 domain with the phospho-Bcr-Abl Y177, is required for activation of these signaling pathways. Therefore, disrupting their interaction represents a potential therapeutic strategy for inhibiting the oncogenic downstream signals of Bcr-Abl. Adenovirus Ad-SH2-HA expressing the Grb2 SH2 domain was constructed and applied in this study. As expected, Ad-SH2-HA efficiently infected CML cells and functioned by binding to the phospho-Bcr-Abl Y177 site, competitively disrupting the Grb2 SH2-phospho-Bcr-Abl Y177 complex. They induced potent anti-proliferation and apoptosis-inducing effects in CML cell lines. Moreover, the Ras, MAPK and Akt activities were significantly reduced in the Ad-SH2-HA treated cells. These were not observed with the point-mutated control adenovirus Ad-Sm-HA with abolished phospho-Bcr-Abl Y177 binding sites. These data indicate that, in addition to the direct targeting of Bcr-Abl, selective inhibition of its downstream signaling pathways may be a therapeutic option for CML, and the Ad-SH2-HA-mediated killing strategy could be explored as a promising anti-leukemia agent in CML.

  19. Cleavage of desmin by cysteine proteases: Calpains and cathepsin B

    DEFF Research Database (Denmark)

    Baron, Caroline; Jacobsen, S.; Purslow, P.P.

    2004-01-01

    The intermediate filament protein, desmin, was purified from pork longissimus dorsi and incubated with either P-calpain, m-calpain or cathepsin B. Proteolysis of desmin was followed using SDS-PAGE and Western blotting. After incubation of desmin with the proteases, cleavage sites on the desmin mo...

  20. Unexpected tolerance of alpha-cleavage of the prion protein to sequence variations.

    Directory of Open Access Journals (Sweden)

    José B Oliveira-Martins

    Full Text Available The cellular form of the prion protein, PrP(C, undergoes extensive proteolysis at the alpha site (109K [see text]H110. Expression of non-cleavable PrP(C mutants in transgenic mice correlates with neurotoxicity, suggesting that alpha-cleavage is important for PrP(C physiology. To gain insights into the mechanisms of alpha-cleavage, we generated a library of PrP(C mutants with mutations in the region neighbouring the alpha-cleavage site. The prevalence of C1, the carboxy adduct of alpha-cleavage, was determined for each mutant. In cell lines of disparate origin, C1 prevalence was unaffected by variations in charge and hydrophobicity of the region neighbouring the alpha-cleavage site, and by substitutions of the residues in the palindrome that flanks this site. Instead, alpha-cleavage was size-dependently impaired by deletions within the domain 106-119. Almost no cleavage was observed upon full deletion of this domain. These results suggest that alpha-cleavage is executed by an alpha-PrPase whose activity, despite surprisingly limited sequence specificity, is dependent on the size of the central region of PrP(C.

  1. The adapter protein, Grb10, is a positive regulator of vascular endothelial growth factor signaling.

    Science.gov (United States)

    Giorgetti-Peraldi, S; Murdaca, J; Mas, J C; Van Obberghen, E

    2001-07-05

    Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis and angiogenesis. Activation of VEGF receptors leads to the recruitment of SH2 containing proteins which link the receptors to the activation of signaling pathways. Here we report that Grb10, an adapter protein of which the biological role remains unknown, is tyrosine phosphorylated in response to VEGF in endothelial cells (HUVEC) and in 293 cells expressing the VEGF receptor KDR. An intact SH2 domain is required for Grb10 tyrosine phosphorylation in response to VEGF, and this phosphorylation is mediated in part through the activation of Src. In HUVEC, VEGF increases Grb10 mRNA level. Expression of Grb10 in HUVEC or in KDR expressing 293 cells results in an increase in the amount and in the tyrosine phosphorylation of KDR. In 293 cells, this is correlated with the activation of signaling molecules, such as MAP kinase. By expressing mutants of Grb10, we found that the positive action of Grb10 is independent of its SH2 domain. Moreover, these Grb10 effects on KDR seem to be specific since Grb10 has no effect on the insulin receptor, and Grb2, another adapter protein, does not mimic the effect of Grb10 on KDR. In conclusion, we propose that VEGF up-regulates Grb10 level, which in turn increases KDR molecules, suggesting that Grb10 could be involved in a positive feedback loop in VEGF signaling.

  2. Calibration and Simulation of the GRB trigger detector of the Ultra Fast Flash Observatory

    DEFF Research Database (Denmark)

    Huang, M.-H.A.; Ahmad, S.; Barrillon, P.

    2013-01-01

    The UFFO (Ultra-Fast Flash Observatory) is a GRB detector on board the Lomonosov satellite, to be launched in 2013. The GRB trigger is provided by an X-ray detector, called UBAT (UFFO Burst Alarm & Trigger Telescope), which detects X-rays from the GRB and then triggers to determine the direction ...

  3. Firework Model: Time Dependent Spectral Evolution of GRB

    Science.gov (United States)

    Barbiellini, Guido; Longo, Francesco; Ghirlanda, G.; Celotti, A.; Bosnjak, Z.

    2004-09-01

    The energetics of the long duration GRB phenomenon is compared with models of a rotating BH in a strong magnetic field generated by an accreting torus. The GRB energy emission is attributed to magnetic field vacuum breakdown that gives origin to a e +/- fireball. Its subsequent evolution is hypothesized in analogy with the in-flight decay of an elementary particle. An anisotropy in the fireball propagation is thus naturally produced. The recent discovery in some GRB of an initial phase characterized by a thermal spectrum could be interpreted as the photon emission of the fireball photosphere when it becomes transparent. In particular, the temporal evolution of the emission can be explained as the effect of a radiative deceleration of the out-moving ejecta.

  4. Short RNA guides cleavage by eukaryotic RNase III.

    Directory of Open Access Journals (Sweden)

    Bruno Lamontagne

    Full Text Available In eukaryotes, short RNAs guide a variety of enzymatic activities that range from RNA editing to translation repression. It is hypothesized that pre-existing proteins evolved to bind and use guide RNA during evolution. However, the capacity of modern proteins to adopt new RNA guides has never been demonstrated. Here we show that Rnt1p, the yeast orthologue of the bacterial dsRNA-specific RNase III, can bind short RNA transcripts and use them as guides for sequence-specific cleavage. Target cleavage occurred at a constant distance from the Rnt1p binding site, leaving the guide RNA intact for subsequent cleavage. Our results indicate that RNase III may trigger sequence-specific RNA degradation independent of the RNAi machinery, and they open the road for a new generation of precise RNA silencing tools that do not trigger a dsRNA-mediated immune response.

  5. GRB 090902B: AFTERGLOW OBSERVATIONS AND IMPLICATIONS

    International Nuclear Information System (INIS)

    Pandey, S. B.; Akerlof, C.; McKay, T. A.; Swenson, C. A.; Perley, D. A.; Kleiser, I. K. W.; Guidorzi, C.; Wiersema, K.; Malesani, D.; Ashley, M. C. B.; Bersier, D.; Cano, Z.; Kobayashi, S.; Melandri, A.; Mottram, C. J.; Gomboc, A.; Ilyin, I.; Jakobsson, P.; Kouveliotou, C.; Levan, A. J.

    2010-01-01

    The optical-infrared afterglow of the Large Area Telescope (LAT)-detected long-duration burst, GRB 090902B, has been observed by several instruments. The earliest detection by ROTSE-IIIa occurred 80 minutes after detection by the Gamma-ray Burst Monitor instrument on board the Fermi Gamma-Ray Space Telescope, revealing a bright afterglow and a decay slope suggestive of a reverse shock origin. Subsequent optical-IR observations followed the light curve for 6.5 days. The temporal and spectral behavior at optical-infrared frequencies is consistent with synchrotron fireball model predictions; the cooling break lies between optical and XRT frequencies ∼1.9 days after the burst. The inferred electron energy index is p = 1.8 ± 0.2, which would however imply an X-ray decay slope flatter than observed. The XRT and LAT data have similar spectral indices and the observed steeper value of the LAT temporal index is marginally consistent with the predicted temporal decay in the radiative regime of the forward shock model. Absence of a jet break during the first 6 days implies a collimation-corrected γ-ray energy E γ > 2.2 x 10 52 erg, one of the highest ever seen in a long-duration gamma-ray bursts. More events combining GeV photon emission with multiwavelength observations will be required to constrain the nature of the central engine powering these energetic explosions and to explore the correlations between energetic quanta and afterglow emission.

  6. Conformation of an Shc-derived phosphotyrosine-containing peptide complexed with the Grb2 SH2 domain

    International Nuclear Information System (INIS)

    Ogura, Kenji; Tsuchiya, Shigeo; Terasawa, Hiroaki; Yuzawa, Satoru; Hatanaka, Hideki; Mandiyan, Valsan; Schlessinger, Joseph; Inagaki, Fuyuhiko

    1997-01-01

    We have determined the structure of an Shc-derived phosphotyrosine-containing peptide complexed with Grb2 SH2 based on intra-and intermolecular NOE correlations observed by a series of isotope-filtered NMR experiments using a PFG z-filter. In contrast to an extended conformation of phosphotyrosine-containing peptides bound to Src, Syp and PLC γ SH2s, the Shc-derived peptide formed a turn at the +1 and +2 positions next to the phosphotyrosine residue. Trp 121 , located at the EF1 site of Grb2 SH2, blocked the peptide binding in an extended conformation. The present study confirms that each phosphotyrosine-containing peptide binds to the cognate SH2 with a specific conformation, which gives the structural basis for the binding specificity between SH2s and target proteins

  7. A novel redox-based switch: LMW-PTP oxidation enhances Grb2 binding and leads to ERK activation

    International Nuclear Information System (INIS)

    Giannoni, Elisa; Raugei, Giovanni; Chiarugi, Paola; Ramponi, Giampietro

    2006-01-01

    Low molecular weight-PTP has been reported as a redox-sensitive protein during both platelet-derived growth factor and integrin signalling. In response to oxidation the phosphatase undergoes a reversible inactivation, which in turn leads to the increase in tyrosine phosphorylation of its substrates and the properly executed anchorage-dependent proliferation program. Here, we report that an exogenous oxidative stress enhances LMW-PTP tyrosine phosphorylation, through oxidation/inactivation of the enzyme, thus preventing its auto-dephosphorylation activity. In particular, we observed a selective hyper-phosphorylation of Tyr132, that acts as a docking site for the adaptor protein Grb2. The redox-dependent enhancement of Grb2 recruitment to LMW-PTP ultimately leads to an improvement of ERK activation, likely triggering a prosurvival signal against the oxidant environment

  8. Flanking signal and mature peptide residues influence signal peptide cleavage

    Directory of Open Access Journals (Sweden)

    Ranganathan Shoba

    2008-12-01

    Full Text Available Abstract Background Signal peptides (SPs mediate the targeting of secretory precursor proteins to the correct subcellular compartments in prokaryotes and eukaryotes. Identifying these transient peptides is crucial to the medical, food and beverage and biotechnology industries yet our understanding of these peptides remains limited. This paper examines the most common type of signal peptides cleavable by the endoprotease signal peptidase I (SPase I, and the residues flanking the cleavage sites of three groups of signal peptide sequences, namely (i eukaryotes (Euk (ii Gram-positive (Gram+ bacteria, and (iii Gram-negative (Gram- bacteria. Results In this study, 2352 secretory peptide sequences from a variety of organisms with amino-terminal SPs are extracted from the manually curated SPdb database for analysis based on physicochemical properties such as pI, aliphatic index, GRAVY score, hydrophobicity, net charge and position-specific residue preferences. Our findings show that the three groups share several similarities in general, but they display distinctive features upon examination in terms of their amino acid compositions and frequencies, and various physico-chemical properties. Thus, analysis or prediction of their sequences should be separated and treated as distinct groups. Conclusion We conclude that the peptide segment recognized by SPase I extends to the start of the mature protein to a limited extent, upon our survey of the amino acid residues surrounding the cleavage processing site. These flanking residues possibly influence the cleavage processing and contribute to non-canonical cleavage sites. Our findings are applicable in defining more accurate prediction tools for recognition and identification of cleavage site of SPs.

  9. Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia virus

    International Nuclear Information System (INIS)

    D'Costa, Susan M.; Antczak, James B.; Pickup, David J.; Condit, Richard C.

    2004-01-01

    Most vaccinia virus intermediate and late mRNAs possess 3' ends that are extremely heterogeneous in sequence. However, late mRNAs encoding the cowpox A-type inclusion protein (ATI), the second largest subunit of the RNA polymerase, and the late telomeric transcripts possess homogeneous 3' ends. In the case of the ATI mRNA, it has been shown that the homogeneous 3' end is generated by a post-transcriptional endoribonucleolytic cleavage event. We have determined that the F17R gene also produces homogeneous transcripts generated by a post-transcriptional cleavage event. Mapping of in vivo mRNA shows that the major 3' end of the F17R transcript maps 1262 nt downstream of the F17R translational start site. In vitro transcripts spanning the in vivo 3' end are cleaved in an in vitro reaction using extracts from virus infected cells, and the site of cleavage is the same both in vivo and in vitro. Cleavage is not observed using extract from cells infected in the presence of hydroxyurea; therefore, the cleavage factor is either virus-coded or virus-induced during the post-replicative phase of virus replication. The cis-acting sequence responsible for cleavage is orientation specific and the factor responsible for cleavage activity has biochemical properties similar to the factor required for cleavage of ATI transcripts. Partially purified cleavage factor generates cleavage products of expected size when either the ATI or F17R substrates are used in vitro, strongly suggesting that cleavage of both transcripts is mediated by the same factor

  10. Time resolved spectroscopy of GRB 030501 using INTEGRAL

    DEFF Research Database (Denmark)

    Beckmann, V.; Borkowski, J.; Courvoisier, T.J.L.

    2003-01-01

    The gamma-ray instruments on-board INTEGRAL offer an unique opportunity to perform time resolved analysis on GRBs. The imager IBIS allows accurate positioning of GRBs and broad band spectral analysis, while SPI provides high resolution spectroscopy. GRB 030501 was discovered by the INTEGRAL Burst...... the Ulysses and RHESSI experiments....

  11. ENERGETIC FERMI/LAT GRB 100414A: ENERGETIC AND CORRELATIONS

    International Nuclear Information System (INIS)

    Urata, Yuji; Tsai, Patrick P.; Huang, Kuiyun; Yamaoka, Kazutaka; Tashiro, Makoto S.

    2012-01-01

    This study presents multi-wavelength observational results for energetic GRB 100414A with GeV photons. The prompt spectral fitting using Suzaku/WAM data yielded spectral peak energies of E src peak of 1458.7 +132.6 –106.6 keV and E iso of 34.5 +2.0 –1.8 × 10 52 erg with z = 1.368. The optical afterglow light curves between 3 and 7 days were effectively fitted according to a simple power law with a temporal index of α = –2.6 ± 0.1. The joint light curve with earlier Swift/UVOT observations yields a temporal break at 2.3 ± 0.2 days. This was the first Fermi/LAT detected event that demonstrated the clear temporal break in the optical afterglow. The jet opening angle derived from this temporal break was 5. 0 8, consistent with those of other well-observed long gamma-ray bursts (GRBs). The multi-wavelength analyses in this study showed that GRB 100414A follows E src peak -E iso and E src peak -E γ correlations. The late afterglow revealed a flatter evolution with significant excesses at 27.2 days. The most straightforward explanation for the excess is that GRB 100414A was accompanied by a contemporaneous supernova. The model light curve based on other GRB-SN events is marginally consistent with that of the observed light curve.

  12. The Supercritical Pile GRB Model: The Prompt to Afterglow Evolution

    Science.gov (United States)

    Mastichiadis, A.; Kazanas, D.

    2009-01-01

    The "Supercritical Pile" is a very economical GRB model that provides for the efficient conversion of the energy stored in the protons of a Relativistic Blast Wave (RBW) into radiation and at the same time produces - in the prompt GRB phase, even in the absence of any particle acceleration - a spectral peak at energy approx. 1 MeV. We extend this model to include the evolution of the RBW Lorentz factor Gamma and thus follow its spectral and temporal features into the early GRB afterglow stage. One of the novel features of the present treatment is the inclusion of the feedback of the GRB produced radiation on the evolution of Gamma with radius. This feedback and the presence of kinematic and dynamic thresholds in the model can be the sources of rich time evolution which we have began to explore. In particular. one can this may obtain afterglow light curves with steep decays followed by the more conventional flatter afterglow slopes, while at the same time preserving the desirable features of the model, i.e. the well defined relativistic electron source and radiative processes that produce the proper peak in the (nu)F(sub nu), spectra. In this note we present the results of a specific set of parameters of this model with emphasis on the multiwavelength prompt emission and transition to the early afterglow.

  13. Early danish GRB experiments - And some for the future?

    DEFF Research Database (Denmark)

    Lund, Niels

    2013-01-01

    by a japanese report of a balloon instrument for GRB studies based on a Rotation Modulation Collimator we at the Danish Space Research Institute started the development of an RMC detector for GRBs, the WATCH wide field monitor. Four WATCH units were flown on the Soviet Granat satellites, and one on ESA's EURECA...

  14. The 1.4 GHZ light curve of GRB 970508

    NARCIS (Netherlands)

    Galama, TJ; Wijers, RAMJ; Groot, PJ; Strom, RG; De Bruyn, AG; Kouveliotou, C; Robinson, CR; van Paradus, J

    1998-01-01

    We report on Westerbork 1.4 GHz radio observations of the radio counterpart to gamma-ray burst GRB 970508, between 0.80 and 138 days after this event. The 1.4 GHz light curve shows a transition from optically thick to thin emission between 39 and 54 days after the event. We derive the slope p of the

  15. GEMINI SPECTROSCOPY OF THE SHORT-HARD GAMMA-RAY BURST GRB 130603B AFTERGLOW AND HOST GALAXY

    Energy Technology Data Exchange (ETDEWEB)

    Cucchiara, A.; Prochaska, J. X.; Werk, J. [Department of Astronomy and Astrophysics, UCO/Lick Observatory, University of California, 1156 High Street, Santa Cruz, CA 95064 (United States); Perley, D.; Cao, Y. [Department of Astronomy, California Institute of Technology, MC 249-17, 1200 East California Blvd, Pasadena, CA 91125 (United States); Cenko, S. B. [Astrophysics Science Division, NASA Goddard Space Flight Center, Greenbelt, MD (United States); Cardwell, A.; Turner, J. [Gemini South Observatory, AURA, Casilla 603, La Serena (Chile); Bloom, J. S. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Cobb, B. E., E-mail: acucchia@ucolick.org [The George Washington University, Washington, DC (United States)

    2013-11-10

    We present early optical photometry and spectroscopy of the afterglow and host galaxy of the bright short-duration gamma-ray burst GRB 130603B discovered by the Swift satellite. Using our Target of Opportunity program on the Gemini South telescope, our prompt optical spectra reveal a strong trace from the afterglow superimposed on continuum and emission lines from the z = 0.3568 ± 0.0005 host galaxy. The combination of a relatively bright optical afterglow (r' = 21.52 at Δt = 8.4 hr), together with an observed offset of 0.''9 from the host nucleus (4.8 kpc projected distance at z = 0.3568), allow us to extract a relatively clean spectrum dominated by afterglow light. Furthermore, the spatially resolved spectrum allows us to constrain the properties of the explosion site directly, and compare these with the host galaxy nucleus, as well as other short-duration GRB host galaxies. We find that while the host is a relatively luminous (L∼0.8 L{sup *}{sub B}), star-forming (SFR = 1.84 M{sub ☉} yr{sup –1}) galaxy with almost solar metallicity, the spectrum of the afterglow exhibits weak Ca II absorption features but negligible emission features. The explosion site therefore lacks evidence of recent star formation, consistent with the relatively long delay time distribution expected in a compact binary merger scenario. The star formation rate (SFR; both in an absolute sense and normalized to the luminosity) and metallicity of the host are both consistent with the known sample of short-duration GRB hosts and with recent results which suggest GRB 130603B emission to be the product of the decay of radioactive species produced during the merging process of a neutron-star-neutron-star binary ({sup k}ilonova{sup )}. Ultimately, the discovery of more events similar to GRB 130603B and their rapid follow-up from 8 m class telescopes will open new opportunities for our understanding of the final stages of compact-objects binary systems and provide crucial

  16. GRB follow-up observations in the East-Asian region

    International Nuclear Information System (INIS)

    Tamagawa, T.; Urata, Y.; Tokyo Institute of Technology, Tokyo; Huang, K. Y.; Ip, W.H.; Qiu, Y.; Hu, J.Y.; Zhou, Xn.; Onda, K.; Tokyo Univ. of Sciences, Tokyo; Makishima, K.; Tokyo Univ., Tokyo

    2005-01-01

    In 2004, we established a Japan-Taiwan-China collaboration for GBR study in the East-Asian region. This serves as a valuable addiction to the world-wide optical and infrared follow-up network, because the East-Asia region would otherwise be blank. We have been carrying out imaging and spectroscopy follow-up observations at Lulin (Taiwan), Kiso (Japan), WIDGET (Japan) and Xinglong (China). From Xinglong and Kiso, we can locate candidates and obtain early time spectra for afterglows. While WIDGET provides early time observations before the bursts, the high-time resolution for multi-band light curves can be obtained at Lulin. With the data from these sites, we can obtain detailed information about the light curve and redshift of GRBs, which are important to understand the mechanism of the afterglows. Up to March 2005, ten follow-up observations have been provided by this East-Asia cooperation. Two optical afterglows were detected, GRB 040924 and GRB 041006. The results of the two detected afterglows are reported in this paper

  17. GRB follow-up observations in the East-Asian region

    Energy Technology Data Exchange (ETDEWEB)

    Tamagawa, T. [RIKEN, Saitama (Japan); Urata, Y. [RIKEN, Saitama (Japan); Tokyo Institute of Technology, Tokyo (Japan). Department of Physics; Huang, K. Y.; Ip, W.H. [National Centre University, Tokyo (Japan). Institute of Astronomy; Qiu, Y.; Hu, J.Y.; Zhou, Xn. [Chinese Academy of Sciences, Beijing (China). National Astronomical Observatoires; Onda, K. [RIKEN, Saitama (Japan); Tokyo Univ. of Sciences, Tokyo (Japan). Department of Physics; Makishima, K. [RIKEN, Saitama (Japan); Tokyo Univ., Tokyo (Japan). Department of Physics

    2005-07-15

    In 2004, we established a Japan-Taiwan-China collaboration for GBR study in the East-Asian region. This serves as a valuable addiction to the world-wide optical and infrared follow-up network, because the East-Asia region would otherwise be blank. We have been carrying out imaging and spectroscopy follow-up observations at Lulin (Taiwan), Kiso (Japan), WIDGET (Japan) and Xinglong (China). From Xinglong and Kiso, we can locate candidates and obtain early time spectra for afterglows. While WIDGET provides early time observations before the bursts, the high-time resolution for multi-band light curves can be obtained at Lulin. With the data from these sites, we can obtain detailed information about the light curve and redshift of GRBs, which are important to understand the mechanism of the afterglows. Up to March 2005, ten follow-up observations have been provided by this East-Asia cooperation. Two optical afterglows were detected, GRB 040924 and GRB 041006. The results of the two detected afterglows are reported in this paper.

  18. Deletion of the Imprinted Gene Grb10 Promotes Hematopoietic Stem Cell Self-Renewal and Regeneration.

    Science.gov (United States)

    Yan, Xiao; Himburg, Heather A; Pohl, Katherine; Quarmyne, Mamle; Tran, Evelyn; Zhang, Yurun; Fang, Tiancheng; Kan, Jenny; Chao, Nelson J; Zhao, Liman; Doan, Phuong L; Chute, John P

    2016-11-01

    Imprinted genes are differentially expressed by adult stem cells, but their functions in regulating adult stem cell fate are incompletely understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an imprinted gene, regulates hematopoietic stem cell (HSC) self-renewal and regeneration. Deletion of the maternal allele of Grb10 in mice (Grb10 m/+ mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10 +/+ mice. After total body irradiation (TBI), Grb10 m/+ mice demonstrated accelerated HSC regeneration and hematopoietic reconstitution, as compared to Grb10 +/+ mice. Grb10-deficient HSCs displayed increased proliferation after competitive transplantation or TBI, commensurate with upregulation of CDK4 and Cyclin E. Furthermore, the enhanced HSC regeneration observed in Grb10-deficient mice was dependent on activation of the Akt/mTORC1 pathway. This study reveals a function for the imprinted gene Grb10 in regulating HSC self-renewal and regeneration and suggests that the inhibition of Grb10 can promote hematopoietic regeneration in vivo. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. The VLT/X-shooter GRB afterglow legacy survey

    Science.gov (United States)

    Kaper, Lex; Fynbo, Johan P. U.; Pugliese, Vanna; van Rest, Daan

    2017-11-01

    The Swift satellite allows us to use gamma-ray bursts (GRBs) to peer through the hearts of star forming galaxies through cosmic time. Our open collaboration, representing most of the active European researchers in this field, builds a public legacy sample of GRB X-shooter spectroscopy while Swift continues to fly. To date, our spectroscopy of more than 100 GRB afterglows covers a redshift range from 0.059 to about 8 (Tanvir et al. 2009, Nature 461, 1254), with more than 20 robust afterglow-based metallicity measurements (over a redshift range from 1.7 to 5.9). With afterglow spectroscopy (throughout the electromagnetic spectrum from X-rays to the sub-mm) we can hence characterize the properties of star-forming galaxies over cosmic history in terms of redshift, metallicity, molecular content, ISM temperature, UV-flux density, etc.. These observations provide key information on the final evolution of the most massive stars collapsing into black holes, with the potential of probing the epoch of the formation of the first (very massive) stars. VLT/X-shooter (Vernet et al. 2011, A&A 536, A105) is in many ways the ideal GRB follow-up instrument and indeed GRB follow-up was one of the primary science cases behind the instrument design and implementation. Due to the wide wavelength coverage of X-shooter, in the same observation one can detect molecular H2 absorption near the atmospheric cut-off and many strong emission lines from the host galaxy in the near-infrared (e.g., Friis et al. 2015, MNRAS 451, 167). For example, we have measured a metallicity of 0.1 Z ⊙ for GRB 100219A at z = 4.67 (Thöne et al. 2013, MNRAS 428, 3590), 0.02 Z ⊙ for GRB 111008A at z = 4.99 (Sparre et al. 2014, ApJ 785, 150) and 0.05 Z ⊙ for GRB 130606A at z = 5.91 (Hartoog et al. 2015, A&A 580, 139). In the latter, the very high value of [Al/Fe]=2.40 +/- 0.78 might be due to a proton capture process and may be a signature of a previous generation of massive (perhaps even the first) stars

  20. Study on corrosion resistance of A106Gr.B and A672Gr.B60 in dynamic water loop with high temperature and pressure

    International Nuclear Information System (INIS)

    Tian Jue; Wang Hui; Li Xinmin

    2014-01-01

    Due to the low carbon and low alloy Cr content, flow accelerates corrosion prone to have a serious impact on safety. AP1000 is the most advanced nuclear power technology in recent years. The plant used A672Gr.B60 as an alternative feed pipe to reduce the impact of flow accelerated corrosion. The impact of different flow rates, alkaline agent type and material property on A672Gr.B60 and A106Gr.B were characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectronic spectroscopy (XPS). After 336 h experiments were conducted, results show that the corrosion rate of A672Gr.B60 is much lower than that of A106Gr.B, and the density of oxidation film on A672Gr.B60 is superior to A106Gr.B. Ethanolamine (ETA) as an alkaline agent is better to reduce FAC to A106Gr.B, and it also can make the oxidation film become denser. Changes in flow rate will affect the size, shape and distribution of the oxide particles, and will also affect the thickness of the oxide film. Both of two materials were composed by Fe 3 O 4 . (authors)

  1. Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

    Science.gov (United States)

    Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

    2016-03-04

    Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

  2. Cleavage and creep fracture of rock salt

    International Nuclear Information System (INIS)

    Chan, K.S.; Munson, D.E.; Bodner, S.R.

    1996-01-01

    The dominant failure mechanism in rock salt at ambient temperature is either cleavage or creep fracture. Since the transition of creep fracture to cleavage in a compressive stress field is not well understood, failure of rock salt by cleavage and creep fracture is analyzed in this paper to elucidate the effect of stress state on the competition between these two fracture mechanisms. For cleavage fracture, a shear crack is assumed to cause the formation and growth of a symmetric pair of wing cracks in a predominantly compressive stress field. The conditions for wing-crack instability are derived and presented as the cleavage fracture boundary in the fracture mechanism map. Using an existing creep fracture model, stress conditions for the onset of creep fracture and isochronous failure curves of specified times-to-rupture are calculated and incorporated into the fracture mechanism map. The regimes of dominance by cleavage and creep fracture are established and compared with experimental data. The result indicates that unstable propagation of cleavage cracks occurs only in the presence of tensile stress. The onset of creep fracture is promoted by a tensile stress, but can be totally suppressed by a high confining pressure. Transition of creep fracture to cleavage occurs when critical conditions of stress difference and tensile stress for crack instability are exceeded

  3. Microstructure and cleavage in lath martensitic steels

    International Nuclear Information System (INIS)

    Morris, John W Jr; Kinney, Chris; Pytlewski, Ken; Adachi, Y

    2013-01-01

    In this paper we discuss the microstructure of lath martensitic steels and the mechanisms by which it controls cleavage fracture. The specific experimental example is a 9Ni (9 wt% Ni) steel annealed to have a large prior austenite grain size, then examined and tested in the as-quenched condition to produce a relatively coarse lath martensite. The microstructure is shown to approximate the recently identified ‘classic’ lath martensite structure: prior austenite grains are divided into packets, packets are subdivided into blocks, and blocks contain interleaved laths whose variants are the two Kurjumov–Sachs relations that share the same Bain axis of the transformation. When the steel is fractured in brittle cleavage, the laths in the block share {100} cleavage planes and cleave as a unit. However, cleavage cracks deflect or blunt at the boundaries between blocks with different Bain axes. It follows that, as predicted, the block size governs the effective grain size for cleavage. (paper)

  4. LFlGRB: Luminosity function of long gamma-ray bursts

    Science.gov (United States)

    Paul, Debdutta

    2018-04-01

    LFlGRB models the luminosity function (LF) of long Gamma Ray Bursts (lGRBs) by using a sample of Swift and Fermi lGRBs to re-derive the parameters of the Yonetoku correlation and self-consistently estimate pseudo-redshifts of all the bursts with unknown redshifts. The GRB formation rate is modeled as the product of the cosmic star formation rate and a GRB formation efficiency for a given stellar mass.

  5. Downstream element determines RNase Y cleavage of the saePQRS operon in Staphylococcus aureus.

    Science.gov (United States)

    Marincola, Gabriella; Wolz, Christiane

    2017-06-02

    In gram-positive bacteria, RNase J1, RNase J2 and RNase Y are thought to be major contributors to mRNA degradation and maturation. In Staphylococcus aureus, RNase Y activity is restricted to regulating the mRNA decay of only certain transcripts. Here the saePQRS operon was used as a model to analyze RNase Y specificity in living cells. A RNase Y cleavage site is located in an intergenic region between saeP and saeQ. This cleavage resulted in rapid degradation of the upstream fragment and stabilization of the downstream fragment. Thereby, the expression ratio of the different components of the operon was shifted towards saeRS, emphasizing the regulatory role of RNase Y activity. To assess cleavage specificity different regions surrounding the sae CS were cloned upstream of truncated gfp, and processing was analyzed in vivo using probes up- and downstream of CS. RNase Y cleavage was not determined by the cleavage site sequence. Instead a 24-bp double-stranded recognition structure was identified that was required to initiate cleavage 6 nt upstream. The results indicate that RNase Y activity is determined by secondary structure recognition determinants, which guide cleavage from a distance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. f (T ) gravity after GW170817 and GRB170817A

    Science.gov (United States)

    Cai, Yi-Fu; Li, Chunlong; Saridakis, Emmanuel N.; Xue, Ling-Qin

    2018-05-01

    The combined observation of GW170817 and its electromagnetic counterpart GRB170817A reveals that gravitational waves propagate at the speed of light in high precision. We apply the standard analysis of cosmological perturbations, as well as the effective field theory approach, to investigate the experimental consequences for the theory of f (T ) gravity. Our analysis verifies for the first time that the speed of gravitational waves within f (T ) gravity is equal to the light speed, and hence, the constraints from GW170817 and GRB170817A are trivially satisfied. Nevertheless, by examining the dispersion relation and the frequency of cosmological gravitational waves, we observe a deviation from the results of general relativity, quantified by a new parameter. Although its value is relatively small in viable f (T ) models, its possible future measurement in advancing gravitational-wave astronomy would be the smoking gun of testing this type of modified gravity.

  7. OBSERVATION OF CORRELATED OPTICAL AND GAMMA EMISSIONS FROM GRB 081126

    International Nuclear Information System (INIS)

    Klotz, A.; Boer, M.; Gendre, B.; Atteia, J. L.; Coward, D. M.; Imerito, A. C.

    2009-01-01

    We present an analysis of time-resolved optical emissions observed from the gamma-ray burst GRB 081126 during the prompt phase. The analysis employed time-resolved photometry using optical data obtained by the TAROT telescope, using BAT data from the Swift spacecraft, and time-resolved spectroscopy at high energies from the GBM instrument onboard the Fermi spacecraft. The optical emission of GRB 081126 is found to be compatible with the second gamma emission pulse shifted by a positive time lag of 8.4 ± 3.9 s. This is the first well-resolved observation of a time lag between optical and gamma emissions during a gamma-ray burst. Our observations could potentially provide new constraints on the fireball model for gamma-ray burst early emissions. Furthermore, observations of time lags between optical and gamma ray photons provides an exciting opportunity to constrain quantum gravity theories.

  8. A Correlated Optical and Gamma Emission from GRB 081126A

    International Nuclear Information System (INIS)

    Gendre, B.; Klotz, A.; Atteia, J. L.; Boeer, M.; Coward, D. M.; Imerito, A. C.

    2010-01-01

    We present an analysis of time-resolved optical emissions observed from the gamma-ray burst GRB 081126 during the prompt phase. The analysis employed time-resolved photometry using optical data obtained by the TAROT telescope, BAT data from the Swift spacecraft and time-resolved spectroscopy at high energies from the GBM instrument onboard the Fermi spacecraft. The optical emission of GRB 081126 is found to be compatible with the second gamma emission pulse shifted by a positive time-lag of 8.4±3.9 sec. This is the first well resolved observation of a time lag between optical and gamma emissions during a gamma-ray burst. Our observations could potentially provide new constraints on the fireball model for gamma ray burst early emissions. Furthermore, observations of time-lags between optical and gamma ray photons provides an exciting opportunity to constrain quantum gravity theories.

  9. ENERGETIC FERMI/LAT GRB 100414A: ENERGETIC AND CORRELATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Urata, Yuji; Tsai, Patrick P. [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Huang, Kuiyun [Academia Sinica Institute of Astronomy and Astrophysics, Taipei 106, Taiwan (China); Yamaoka, Kazutaka [Department of Physics and Mathematics, Aoyama Gakuin University, 5-10-1, Fuchinobe, Sayamihara 229-8558 (Japan); Tashiro, Makoto S., E-mail: urata@astro.ncu.edu.tw [Department of Physics, Saitama University, Shimo-Okubo, Saitama 338-8570 (Japan)

    2012-03-20

    This study presents multi-wavelength observational results for energetic GRB 100414A with GeV photons. The prompt spectral fitting using Suzaku/WAM data yielded spectral peak energies of E{sup src}{sub peak} of 1458.7{sup +132.6}{sub -106.6} keV and E{sub iso} of 34.5{sup +2.0}{sub -1.8} Multiplication-Sign 10{sup 52} erg with z = 1.368. The optical afterglow light curves between 3 and 7 days were effectively fitted according to a simple power law with a temporal index of {alpha} = -2.6 {+-} 0.1. The joint light curve with earlier Swift/UVOT observations yields a temporal break at 2.3 {+-} 0.2 days. This was the first Fermi/LAT detected event that demonstrated the clear temporal break in the optical afterglow. The jet opening angle derived from this temporal break was 5.{sup 0}8, consistent with those of other well-observed long gamma-ray bursts (GRBs). The multi-wavelength analyses in this study showed that GRB 100414A follows E{sup src}{sub peak}-E{sub iso} and E{sup src}{sub peak}-E{sub {gamma}} correlations. The late afterglow revealed a flatter evolution with significant excesses at 27.2 days. The most straightforward explanation for the excess is that GRB 100414A was accompanied by a contemporaneous supernova. The model light curve based on other GRB-SN events is marginally consistent with that of the observed light curve.

  10. THE LATE PEAKING AFTERGLOW OF GRB 100418A

    International Nuclear Information System (INIS)

    Marshall, F. E.; Holland, S. T.; Sakamoto, T.; Antonelli, L. A.; Burrows, D. N.; Siegel, M. H.; Covino, S.; Fugazza, D.; De Pasquale, M.; Oates, S. R.; Evans, P. A.; O'Brien, P. T.; Osborne, J. P.; Pagani, C.; Liang, E. W.; Wu, X. F.; Zhang, B.

    2011-01-01

    GRB 100418A is a long gamma-ray burst (GRB) at redshift z = 0.6235 discovered with the Swift Gamma-ray Burst Explorer with unusual optical and X-ray light curves. After an initial short-lived, rapid decline in X-rays, the optical and X-ray light curves observed with Swift are approximately flat or rising slightly out to at least ∼7 x 10 3 s after the trigger, peak at ∼5 x 10 4 s, and then follow an approximately power-law decay. Such a long optical plateau and late peaking is rarely seen in GRB afterglows. Observations with Rapid Eye Mount during a gap in the Swift coverage indicate a bright optical flare at ∼2.5 x 10 4 s. The long plateau phase of the afterglow is interpreted using either a model with continuous injection of energy into the forward shock of the burst or a model in which the jet of the burst is viewed off-axis. In both models the isotropic kinetic energy in the late afterglow after the plateau phase is ≥10 2 times the 10 51 erg of the prompt isotropic gamma-ray energy release. The energy injection model is favored because the off-axis jet model would require the intrinsic T 90 for the GRB jet viewed on-axis to be very short, ∼10 ms, and the intrinsic isotropic gamma-ray energy release and the true jet energy to be much higher than the typical values of known short GRBs. The non-detection of a jet break up to t ∼ 2 x 10 6 s indicates a jet half-opening angle of at least ∼14 0 , and a relatively high-collimation-corrected jet energy of E jet ≥ 10 52 erg.

  11. Fermi-LAT Observations of the Gamma-Ray Burst GRB 130427A

    Science.gov (United States)

    Ackermann, M.; Ajello, M.; Asano, K.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Baring, M. G.; Bastieri, D.; hide

    2013-01-01

    The observations of the exceptionally bright gamma-ray burst (GRB) 130427A by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources. GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest gamma-ray duration (20 hours), and one of the largest isotropic energy releases ever observed from a GRB. Temporal and spectral analyses of GRB 130427A challenge the widely accepted model that the nonthermal high-energy emission in the afterglow phase of GRBs is synchrotron emission radiated by electrons accelerated at an external shock.

  12. Spitzer Observations of GRB Hosts: A Legacy Approach

    Science.gov (United States)

    Perley, Daniel; Tanvir, Nial; Hjorth, Jens; Berger, Edo; Laskar, Tanmoy; Michalowski, Michal; Chary, Ranga-Ram; Fynbo, Johan; Levan, Andrew

    2012-09-01

    The host galaxies of long-duration GRBs are drawn from uniquely broad range of luminosities and redshifts. Thus they offer the possibility of studying the evolution of star-forming galaxies without the limitations of other luminosity-selected samples, which typically are increasingly biased towards the most massive systems at higher redshift. However, reaping the full benefits of this potential requires careful attention to the selection biases affecting host identification. To this end, we propose observations of a Legacy sample of 70 GRB host galaxies (an additional 70 have already been observed by Spitzer), in order to constrain the mass and luminosity function in GRB-selected galaxies at high redshift, including its dependence on redshift and on properties of the afterglow. Crucially, and unlike previous Spitzer surveys, this sample is carefully designed to be uniform and free of optical selection biases that have caused previous surveys to systematically under-represent the role of luminous, massive hosts. We also propose to extend to larger, more powerfully constraining samples the study of two science areas where Spitzer observations have recently shown spectacular success: the hosts of dust-obscured GRBs (which promise to further our understanding of the connection between GRBs and star-formation in the most luminous galaxies), and the evolution of the mass-metallicity relation at z>2 (for which GRB host observations provide particularly powerful constraints on high-z chemical evolution).

  13. Cleavage and Cell Adhesion Properties of Human Epithelial Cell Adhesion Molecule (HEPCAM)*

    Science.gov (United States)

    Tsaktanis, Thanos; Kremling, Heidi; Pavšič, Miha; von Stackelberg, Ricarda; Mack, Brigitte; Fukumori, Akio; Steiner, Harald; Vielmuth, Franziska; Spindler, Volker; Huang, Zhe; Jakubowski, Jasmine; Stoecklein, Nikolas H.; Luxenburger, Elke; Lauber, Kirsten; Lenarčič, Brigita; Gires, Olivier

    2015-01-01

    Human epithelial cell adhesion molecule (HEPCAM) is a tumor-associated antigen frequently expressed in carcinomas, which promotes proliferation after regulated intramembrane proteolysis. Here, we describe extracellular shedding of HEPCAM at two α-sites through a disintegrin and metalloprotease (ADAM) and at one β-site through BACE1. Transmembrane cleavage by γ-secretase occurs at three γ-sites to generate extracellular Aβ-like fragments and at two ϵ-sites to release human EPCAM intracellular domain HEPICD, which is efficiently degraded by the proteasome. Mapping of cleavage sites onto three-dimensional structures of HEPEX cis-dimer predicted conditional availability of α- and β-sites. Endocytosis of HEPCAM warrants acidification in cytoplasmic vesicles to dissociate protein cis-dimers required for cleavage by BACE1 at low pH values. Intramembrane cleavage sites are accessible and not part of the structurally important transmembrane helix dimer crossing region. Surprisingly, neither chemical inhibition of cleavage nor cellular knock-out of HEPCAM using CRISPR-Cas9 technology impacted the adhesion of carcinoma cell lines. Hence, a direct function of HEPCAM as an adhesion molecule in carcinoma cells is not supported and appears to be questionable. PMID:26292218

  14. Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products

    Directory of Open Access Journals (Sweden)

    Jack Xie

    2010-08-01

    Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.

  15. Sequence specificity of DNA cleavage by Micrococcus luteus γ endonuclease

    International Nuclear Information System (INIS)

    Hentosh, P.; Henner, W.D.; Reynolds, R.J.

    1985-01-01

    DNA fragments of defined sequence have been used to determine the sites of cleavage by γ-endonuclease activity in extracts prepared from Micrococcus luteus. End-labeled DNA restriction fragments of pBR322 DNA that had been irradiated under nitrogen in the presence of potassium iodide or t-butanol were treated with M. luteus γ endonuclease and analyzed on irradiated DNA preferentially at the positions of cytosines and thymines. DNA cleavage occurred immediately to the 3' side of pyrimidines in irradiated DNA and resulted in fragments that terminate in a 5'-phosphoryl group. These studies indicate that both altered cytosines and thymines may be important DNA lesions requiring repair after exposure to γ radiation

  16. The GRB 060218/SN 2006aj event in the context of other gamma-ray burst supernovae

    DEFF Research Database (Denmark)

    Ferrero, P.; Kann, D. A.; Zeh, A.

    2006-01-01

    Gamma rays: bursts: X-rays: individuals: GRB 060218, supernovae: individual: SN 2006aj Udgivelsesdato: Oct.......Gamma rays: bursts: X-rays: individuals: GRB 060218, supernovae: individual: SN 2006aj Udgivelsesdato: Oct....

  17. Short-hairpin RNA-mediated stable silencing of Grb2 impairs cell growth and DNA synthesis

    International Nuclear Information System (INIS)

    Di Fulvio, Mauricio; Henkels, Karen M.; Gomez-Cambronero, Julian

    2007-01-01

    Grb2 is an SH2-SH3 protein adaptor responsible for linking growth factor receptors with intracellular signaling cascades. To study the role of Grb2 in cell growth, we have generated a new COS7 cell line (COS7 shGrb2 ), based on RNAi technology, as null mutations in mammalian Grb2 genes are lethal in early development. This novel cell line continuously expresses a short hairpin RNA that targets endogenous Grb2. Stable COS7 shGrb2 cells had the shGrb2 integrated into the genomic DNA and carried on SiL construct (made refractory to the shRNA-mediated interference), but not with an SH2-deficient mutant (R86K). Thus, a viable knock-down and rescue protocol has demonstrated that Grb2 is crucial for cell proliferation

  18. GRB 161219B / SN 2016jca: A low-redshift gamma-ray burst supernova powered by radioactive heating

    DEFF Research Database (Denmark)

    Cano, Z.; Izzo, L.; De Ugarte Postigo, A.

    2017-01-01

    Since the first discovery of a broad-lined type Ic supernova (SN) with a long-duration gamma-ray burst (GRB) in 1998, fewer than fifty gamma-ray burst supernovae (GRB-SNe) have been discovered. The intermediate-luminosity Swift GRB 161219B and its associated supernova SN 2016jca, which occurred a...

  19. Fermi-LAT Observations of the Gamma-Ray Burst GRB 130427A

    NARCIS (Netherlands)

    Ackermann, M.; et al., [Unknown; van der Horst, A.J.

    2014-01-01

    The observations of the exceptionally bright gamma-ray burst (GRB) 130427A by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources. GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest

  20. Spatially-resolved dust properties of the GRB 980425 host galaxy

    DEFF Research Database (Denmark)

    Michałowski, Michał J.; Hunt, L. K.; Palazzi, E.

    2014-01-01

    ), located 800 pc away from the GRB position. The host is characterised by low dust content and high fraction of UV-visible star-formation, similar to other dwarf galaxies. Such galaxies are abundant in the local universe, so it is not surprising to find a GRB in one of them, assuming the correspondence...

  1. A metal-rich molecular cloud surrounds GRB 050904 at redshift 6.3

    NARCIS (Netherlands)

    Campana, S.; Lazzati, D.; Ripamonti, Emanuele; Perna, R.; Covino, S.; Tagliaferri, G.; Moretti, A.; Romano, P.; Cusumano, G.; Chincarini, G.

    2007-01-01

    GRB 050904 is the gamma-ray burst with the highest measured redshift. We performed time-resolved X-ray spectroscopy of the late GRB and early afterglow emission. We find robust evidence for a decrease with time of the soft X-ray-absorbing column. We model the evolution of the column density due to

  2. Multiwavelength analysis of the intriguing GRB 061126: The reverse shock scenario and magnetization

    NARCIS (Netherlands)

    Gomboc, A.; Kobayashi, S.; Guidorzi, C.; Melandri, A.; Mangano, V.; Sbarufatti, B.; Mundell, C.G.; Schady, P.; Smith, R.J.; Updike, A.C.; Kann, D.A.; Misra, K.; Rol, E.; Pozanenko, A.; Castro-Tirado, A.J.; Anupama, G.C.; Bersier, D.; Bode, M.F.; Carter, D.; Curran, P.; Fruchter, A.; Graham, J.; Hartmann, D.H.; Ibrahimov, M.; Levan, A.; Monfardini, A.; Mottram, C.J.; O'Brien, P.T.; Prema, P.; Sahu, D.K.; Steele, I.A.; Tanvir, N.R.; Wiersema, K.

    2008-01-01

    We present a detailed study of the prompt and afterglow emission from Swift GRB 061126 using BAT, XRT, UVOT data and multicolor optical imaging from 10 ground-based telescopes. GRB 061126 was a long burst (T90 = 191 s) with four overlapping peaks in its γ-ray light curve. The X-ray afterglow,

  3. The prompt to late-time multiwavelength analysis of GRB 060210

    NARCIS (Netherlands)

    Curran, P.A.; van der Horst, A.J.; Beardmore, A.P.; Page, K.L.; Rol, E.; Melandri, A.; Steele, I.A.; Mundell, C.G.; Gomboc, A.; O'Brien, P.T.; Bersier, D.F.; Bode, M.F.; Carter, D.; Guidorzi, C.; Hill, J.E.; Hurkett, C.P.; Kobayashi, S.; Monfardini, A.; Mottram, C.J.; Smith, R.J.; Wijers, R.A.M.J.; Willingale, R.

    2007-01-01

    Aims.We present our analysis of the multiwavelength photometric & spectroscopic observations of GRB 060210 and discuss the results in the overall context of current GRB models. Methods: All available optical data underwent a simultaneous temporal fit, while X-ray and gamma-ray observations were

  4. Broadband Study of GRB 091127: A Sub-energetic Burst at Higher Redshift?

    Science.gov (United States)

    Troja, E.; Sakamoto, T.; Guidorzi, C.; Norris, J. P.; Panaitescu, A.; Kobayashi, S.; Omodei, N.; Brown, J. C.; Burrows, D. N.; Evans, P. A.; Gehrels, N.; Marshall, F. E.; Mawson, N.; Melandri, A.; Mundell, C. G.; Oates, S. R.; Pal'shin, V.; Preece, R. D.; Racusin, J. L.; Steele, I. A.; Tanvir, N. R.; Vasileiou, V.; Wilson-Hodge, C.; Yamaoka, K.

    2012-12-01

    GRB 091127 is a bright gamma-ray burst (GRB) detected by Swift at a redshift z = 0.49 and associated with SN 2009nz. We present the broadband analysis of the GRB prompt and afterglow emission and study its high-energy properties in the context of the GRB/SN association. While the high luminosity of the prompt emission and standard afterglow behavior are typical of cosmological long GRBs, its low-energy release (E γ < 3 × 1049 erg), soft spectrum, and unusual spectral lag connect this GRB to the class of sub-energetic bursts. We discuss the suppression of high-energy emission in this burst, and investigate whether this behavior could be connected with the sub-energetic nature of the explosion.

  5. BROADBAND STUDY OF GRB 091127: A SUB-ENERGETIC BURST AT HIGHER REDSHIFT?

    Energy Technology Data Exchange (ETDEWEB)

    Troja, E.; Sakamoto, T.; Brown, J. C.; Gehrels, N.; Marshall, F. E.; Racusin, J. L. [NASA, Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Guidorzi, C. [Physics Department, University of Ferrara, via Saragat 1, I-44122, Ferrara (Italy); Norris, J. P. [Physics Department, Boise State University, 1910 University Drive, Boise, ID 83725 (United States); Panaitescu, A. [Space Science and Applications, MS D466, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Kobayashi, S.; Mawson, N.; Melandri, A.; Mundell, C. G.; Steele, I. A. [Astrophysics Research Institute, Liverpool John Moores University, Twelve Quays House, Egerton Wharf, CH41 1LD Birkenhead (United Kingdom); Omodei, N. [W. W. Hansen Experimental Physics Laboratory, Kavli Institute for Particle Astrophysics and Cosmology, Department of Physics and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States); Burrows, D. N. [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Evans, P. A. [X-ray and Observational Astronomy Group, Department of Physics and Astronomy, University of Leicester, Leicester LE1 7RH (United Kingdom); Oates, S. R. [Mullard Space Science Laboratory, University College London, Holmbury St. Mary, Dorking, Surrey RH5 6NT (United Kingdom); Pal' shin, V. [Ioffe Physico-Technical Institute, Laboratory for Experimental Astrophysics, 26 Polytekhnicheskaya, St Petersburg 194021 (Russian Federation); Preece, R. D. [Department of Physics, University of Alabama in Huntsville, NSSTC, 320 Sparkman Drive, Huntsville, AL 35805 (United States); and others

    2012-12-10

    GRB 091127 is a bright gamma-ray burst (GRB) detected by Swift at a redshift z = 0.49 and associated with SN 2009nz. We present the broadband analysis of the GRB prompt and afterglow emission and study its high-energy properties in the context of the GRB/SN association. While the high luminosity of the prompt emission and standard afterglow behavior are typical of cosmological long GRBs, its low-energy release (E{sub {gamma}} < 3 Multiplication-Sign 10{sup 49} erg), soft spectrum, and unusual spectral lag connect this GRB to the class of sub-energetic bursts. We discuss the suppression of high-energy emission in this burst, and investigate whether this behavior could be connected with the sub-energetic nature of the explosion.

  6. Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

    International Nuclear Information System (INIS)

    Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Burke, Terrence R.; Inagaki, Fuyuhiko

    2008-01-01

    The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity

  7. Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

    Science.gov (United States)

    Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

    2016-02-23

    In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL.

  8. On the formation and nature of quasi-cleavage fracture surfaces in hydrogen embrittled steels

    Energy Technology Data Exchange (ETDEWEB)

    Martin, May L.; Fenske, Jamey A.; Liu, Grace S.; Sofronis, Petros [University of Illinois, Dept. of Materials Science and Engineering, 1304 W. Green St., Urbana, IL 61801 (United States); Robertson, Ian M., E-mail: ianr@illinois.edu [University of Illinois, Dept. of Materials Science and Engineering, 1304 W. Green St., Urbana, IL 61801 (United States)

    2011-02-15

    Quasi-cleavage, a common feature of hydrogen-induced fracture surfaces, is generally taken as being cleavage-like but not along a known cleavage plane. Despite the frequency with which this surface is observed, the relationship to the underlying microstructure remains unknown. Through a combination of topographical reconstruction of secondary electron microscope fractographs and a transmission electron microscopy study of the microstructure from site-specific locations, it will be shown that the features on quasi-cleavage surfaces are ridges that can be correlated with sub-surface intense and highly localized deformation bands. It will be demonstrated that the fracture surface arises from the growth and coalescence of voids that initiate at and extend along slip band intersections. This mechanism and process is fully consistent with hydrogen enhancing and localizing plastic processes.

  9. Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein.

    Science.gov (United States)

    Welch, Brett D; Liu, Yuanyuan; Kors, Christopher A; Leser, George P; Jardetzky, Theodore S; Lamb, Robert A

    2012-10-09

    The paramyxovirus parainfluenza virus 5 (PIV5) enters cells by fusion of the viral envelope with the plasma membrane through the concerted action of the fusion (F) protein and the receptor binding protein hemagglutinin-neuraminidase. The F protein folds initially to form a trimeric metastable prefusion form that is triggered to undergo large-scale irreversible conformational changes to form the trimeric postfusion conformation. It is thought that F refolding couples the energy released with membrane fusion. The F protein is synthesized as a precursor (F0) that must be cleaved by a host protease to form a biologically active molecule, F1,F2. Cleavage of F protein is a prerequisite for fusion and virus infectivity. Cleavage creates a new N terminus on F1 that contains a hydrophobic region, known as the FP, which intercalates target membranes during F protein refolding. The crystal structure of the soluble ectodomain of the uncleaved form of PIV5 F is known; here we report the crystal structure of the cleavage-activated prefusion form of PIV5 F. The structure shows minimal movement of the residues adjacent to the protease cleavage site. Most of the hydrophobic FP residues are buried in the uncleaved F protein, and only F103 at the newly created N terminus becomes more solvent-accessible after cleavage. The conformational freedom of the charged arginine residues that compose the protease recognition site increases on cleavage of F protein.

  10. THE OPTICALLY UNBIASED GRB HOST (TOUGH) SURVEY. III. REDSHIFT DISTRIBUTION

    Energy Technology Data Exchange (ETDEWEB)

    Jakobsson, P.; Chapman, R.; Vreeswijk, P. M. [Centre for Astrophysics and Cosmology, Science Institute, University of Iceland, Dunhagi 5, 107 Reykjavik (Iceland); Hjorth, J.; Malesani, D.; Fynbo, J. P. U.; Milvang-Jensen, B. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, 2100 Copenhagen (Denmark); Tanvir, N. R.; Starling, R. L. C. [Department of Physics and Astronomy, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Letawe, G. [Departement d' Astrophysique, Geophysique et Oceanographie, ULg, Allee du 6 aout, 17-Bat. B5c B-4000 Liege (Sart-Tilman) (Belgium)

    2012-06-10

    We present 10 new gamma-ray burst (GRB) redshifts and another five redshift limits based on host galaxy spectroscopy obtained as part of a large program conducted at the Very Large Telescope (VLT). The redshifts span the range 0.345 {<=} z {approx}< 2.54. Three of our measurements revise incorrect values from the literature. The homogeneous host sample researched here consists of 69 hosts that originally had a redshift completeness of 55% (with 38 out of 69 hosts having redshifts considered secure). Our project, including VLT/X-shooter observations reported elsewhere, increases this fraction to 77% (53/69), making the survey the most comprehensive in terms of redshift completeness of any sample to the full Swift depth, analyzed to date. We present the cumulative redshift distribution and derive a conservative, yet small, associated uncertainty. We constrain the fraction of Swift GRBs at high redshift to a maximum of 14% (5%) for z > 6 (z > 7). The mean redshift of the host sample is assessed to be (z) {approx}> 2.2, with the 10 new redshifts reducing it significantly. Using this more complete sample, we confirm previous findings that the GRB rate at high redshift (z {approx}> 3) appears to be in excess of predictions based on assumptions that it should follow conventional determinations of the star formation history of the universe, combined with an estimate of its likely metallicity dependence. This suggests that either star formation at high redshifts has been significantly underestimated, for example, due to a dominant contribution from faint, undetected galaxies, or that GRB production is enhanced in the conditions of early star formation, beyond that usually ascribed to lower metallicity.

  11. Swift captures the spectrally evolving prompt emission of GRB070616

    Science.gov (United States)

    Starling, R. L. C.; O'Brien, P. T.; Willingale, R.; Page, K. L.; Osborne, J. P.; de Pasquale, M.; Nakagawa, Y. E.; Kuin, N. P. M.; Onda, K.; Norris, J. P.; Ukwatta, T. N.; Kodaka, N.; Burrows, D. N.; Kennea, J. A.; Page, M. J.; Perri, M.; Markwardt, C. B.

    2008-02-01

    The origins of gamma-ray burst (GRB) prompt emission are currently not well understood and in this context long, well-observed events are particularly important to study. We present the case of GRB070616, analysing the exceptionally long-duration multipeaked prompt emission, and later afterglow, captured by all the instruments on-board Swift and by Suzaku Wide-Band All-Sky Monitor (WAM). The high-energy light curve remained generally flat for several hundred seconds before going into a steep decline. Spectral evolution from hard to soft is clearly taking place throughout the prompt emission, beginning at 285s after the trigger and extending to 1200s. We track the movement of the spectral peak energy, whilst observing a softening of the low-energy spectral slope. The steep decline in flux may be caused by a combination of this strong spectral evolution and the curvature effect. We investigate origins for the spectral evolution, ruling out a superposition of two power laws and considering instead an additional component dominant during the late prompt emission. We also discuss origins for the early optical emission and the physics of the afterglow. The case of GRB070616 clearly demonstrates that both broad-band coverage and good time resolution are crucial to pin down the origins of the complex prompt emission in GRBs. This paper is dedicated to the memory of Dr Francesca Tamburelli who died during its production. Francesca played a fundamental role within the team which is in charge of the development of the Swift X-Ray Telescope (XRT) data analysis software at the Italian Space Agency's Science Data Centre in Frascati. She is sadly missed. E-mail: rlcs1@star.le.ac.uk

  12. The bright optical afterglow of the long GRB 001007

    DEFF Research Database (Denmark)

    Ceron, J.M.C.; Castro-Tirado, A.J.; Gorosabel, J.

    2002-01-01

    We present optical follow up observations of the long GRB 001007 between 6.14 hours and similar to468 days after the event. An unusually bright optical afterglow (OA) was seen to decline following a steep power law decay with index alpha = -2.03 +/- 0.11, possibly indicating a break in the light...... curve at t - t(0) hours after the gamma ray event provide tentative (1.2σ) evidence for a break in the optical light curve. The spectral index β of the OA yields -1.24 +/- 0.57. These values may be explained both...

  13. Light speed variation from gamma ray burst GRB 160509A

    Directory of Open Access Journals (Sweden)

    Haowei Xu

    2016-09-01

    Full Text Available It is postulated in Einstein's relativity that the speed of light in vacuum is a constant for all observers. However, the effect of quantum gravity could bring an energy dependence of light speed. Even a tiny speed variation, when amplified by the cosmological distance, may be revealed by the observed time lags between photons with different energies from astrophysical sources. From the newly detected long gamma ray burst GRB 160509A, we find evidence to support the prediction for a linear form modification of light speed in cosmological space.

  14. Light speed variation from gamma ray burst GRB 160509A

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Haowei [School of Physics, State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China); Ma, Bo-Qiang, E-mail: mabq@pku.edu.cn [School of Physics, State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China); Collaborative Innovation Center of Quantum Matter, Beijing (China); Center for High Energy Physics, Peking University, Beijing 100871 (China); Center for History and Philosophy of Science, Peking University, Beijing 100871 (China)

    2016-09-10

    It is postulated in Einstein's relativity that the speed of light in vacuum is a constant for all observers. However, the effect of quantum gravity could bring an energy dependence of light speed. Even a tiny speed variation, when amplified by the cosmological distance, may be revealed by the observed time lags between photons with different energies from astrophysical sources. From the newly detected long gamma ray burst GRB 160509A, we find evidence to support the prediction for a linear form modification of light speed in cosmological space.

  15. The blue host galaxy of the red GRB 000418

    DEFF Research Database (Denmark)

    Gorosabel, J.; Klose, S.; Christensen, L.

    2003-01-01

    We report on multi-band (UBVRIZJ(s)K(s)) observations of the host galaxy of the April 18, 2000 gamma-ray burst. The Spectral Energy Distribution (SED) is analysed by fitting empirical and synthetic spectral templates. We find that: (i) the best SED fit is obtained with a starburst template, (ii) ...... structures (like dust lanes, spiral arms or disks). A natural scenario which accounts of all the above results is a nuclear starburst that harbours a young population of stars from which the GRB originated....

  16. Four Years of Observations of GRB Localizations with TAROT

    International Nuclear Information System (INIS)

    Boeer, M.; Thiebaud, C.; Atteia, J.-L.; Malina, R.; Freitas Pacheco, J. de; Pedersen, H.; Klotz, A.

    2004-01-01

    We present a summary of the observations performed with the Telescope a Action Rapide pour les Objets Transitoires (TAROT - Rapid Action Telescope for Transient Objects) performed over the period 1999 - 2003. Seventeen GRB localization observations where performed shortly after the burst (10s - 90min.), and in at least one case, even while the source was still active in gamma-rays. During this period CGRO. HETE-2 and INTEGRAL were in operation. Though no alert was missed, no source was detected, to a magnitude limit between R = 15 and R = 20. Future plans are also presented, featuring the duplication of TAROT at ESO - La Silla

  17. Programmable RNA recognition and cleavage by CRISPR/Cas9.

    Science.gov (United States)

    O'Connell, Mitchell R; Oakes, Benjamin L; Sternberg, Samuel H; East-Seletsky, Alexandra; Kaplan, Matias; Doudna, Jennifer A

    2014-12-11

    The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA-DNA complementarity to identify target sites for sequence-specific double-stranded DNA (dsDNA) cleavage. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, known as the protospacer adjacent motif (PAM), next to and on the strand opposite the twenty-nucleotide target site in dsDNA. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in a large range of prokaryotic and eukaryotic cell types, and in whole organisms, but it has been thought to be incapable of targeting RNA. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalysed DNA cleavage. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous messenger RNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable transcript recognition without the need for tags.

  18. THE PROPERTIES OF THE 2175 Å EXTINCTION FEATURE DISCOVERED IN GRB AFTERGLOWS

    International Nuclear Information System (INIS)

    Zafar, Tayyaba; Watson, Darach; Elíasdóttir, Árdís; Fynbo, Johan P. U.; Krühler, Thomas; Leloudas, Giorgos; Schady, Patricia; Greiner, Jochen; Jakobsson, Páll; Thöne, Christina C.; Perley, Daniel A.; Morgan, Adam N.; Bloom, Joshua

    2012-01-01

    The unequivocal, spectroscopic detection of the 2175 Å bump in extinction curves outside the Local Group is rare. To date, the properties of the bump have been examined in only two gamma-ray burst (GRB) afterglows (GRB 070802 and GRB 080607). In this work, we analyze in detail the detections of the 2175 Å extinction bump in the optical spectra of two further GRB afterglows: GRB 080605 and 080805. We gather all available optical/near-infrared photometric, spectroscopic, and X-ray data to construct multi-epoch spectral energy distributions (SEDs) for both GRB afterglows. We fit the SEDs with the Fitzpatrick and Massa model with a single or broken power law. We also fit a sample of 38 GRB afterglows, known to prefer a Small Magellanic Cloud (SMC)-type extinction curve, with the same model. We find that the SEDs of GRB 080605 and GRB 080805 at two epochs are fit well with a single power law with a derived extinction of A V = 0.52 +0.13 –0.16 and 0.50 +0.13 –0.10 , and 2.1 +0.7 –0.6 and 1.5 ± 0.2, respectively. While the slope of the extinction curve of GRB 080805 is not well constrained, the extinction curve of GRB 080605 has an unusual very steep far-UV rise together with the 2175 Å bump. Such an extinction curve has previously been found in only a small handful of sightlines in the Milky Way. One possible explanation of such an extinction curve may be dust arising from two different regions with two separate grain populations, however we cannot distinguish the origin of the curve. We finally compare the four 2175 Å bump sightlines to the larger GRB afterglow sample and to Local Group sightlines. We find that while the width and central positions of the bumps are consistent with what is observed in the Local Group, the relative strength of the detected bump (A bump ) for GRB afterglows is weaker for a given A V than for almost any Local Group sightline. Such dilution of the bump strength may offer tentative support to a dual dust-population scenario.

  19. IceCube and GRB neutrinos propagating in quantum spacetime

    Directory of Open Access Journals (Sweden)

    Giovanni Amelino-Camelia

    2016-10-01

    Full Text Available Two recent publications have reported intriguing analyses, tentatively suggesting that some aspects of IceCube data might be manifestations of quantum-gravity-modified laws of propagation for neutrinos. We here propose a strategy of data analysis which has the advantage of being applicable to several alternative possibilities for the laws of propagation of neutrinos in a quantum spacetime. In all scenarios here of interest one should find a correlation between the energy of an observed neutrino and the difference between the time of observation of that neutrino and the trigger time of a GRB. We select accordingly some GRB-neutrino candidates among IceCube events, and our data analysis finds a rather strong such correlation. This sort of study naturally lends itself to the introduction of a “false alarm probability”, which for our analysis we estimate conservatively to be of 1%. We therefore argue that our findings should motivate a vigorous program of investigation following the strategy here advocated.

  20. Relativistic hydrodynamic simulation of jet deceleration in GRB

    International Nuclear Information System (INIS)

    Meliani, Z.; Keppens, R.; Casse, F.

    2008-01-01

    Using the novel adaptive mesh refinement code, AMRVAC, we investigate the interaction between collimated ejecta (jetlike fireball models with various opening angle) with its surrounding cold Interstellar Medium (ISM). This is relevant for Gamma Ray Bursts, and we demonstrate that, thanks to the AMR strategy, we resolve the internal structure of the shocked shell-ISM matter. We determine the deceleration from an initial Lorentz factor γ = 100 up to the almost Newtonian γ∼O(3) phase of the flow. We discuss the effect of varying the opening angle on the deceleration, and pay attention to differences with their 1D isotropic GRB equivalents. These are due to thermally induced sideways expansions of both shocked shell and shocked ISM regions. The propagating 2D ultrarelativistic shell does not accrete all the surrounding medium located within its initial opening angle. The difference with isotropic GRB models is quite pronounced for shells with small opening angle. In the most collimated ejecta (open angle of 1 deg.), the deceleration phase (once the reverse shock has traversed the shell structure) shows distinct modulation, attributed to repeated rarefactions traversing the shell. These may have a clear impact on the emitted afterglow radiation

  1. ON THE NEUTRINO NON-DETECTION OF GRB 130427A

    Energy Technology Data Exchange (ETDEWEB)

    Gao Shan; Kashiyama, Kazumi; Meszaros, Peter, E-mail: sxg324@psu.edu, E-mail: kzk15@psu.edu, E-mail: pmeszaros@astro.psu.edu [Department of Physics, Department of Astronomy and Astrophysics, Center for Particle Astrophysics, Pennsylvania State University, University Park, PA 16802 (United States)

    2013-07-20

    The recent gamma-ray burst GRB 130427A has an isotropic electromagnetic energy E{sup iso} {approx} 10{sup 54} erg, suggesting an ample supply of target photons for photo-hadronic interactions, which at its low redshift of z {approx} 0.34 would appear to make it a promising candidate for neutrino detection. However, the IceCube collaboration has reported a null result based on a search during the prompt emission phase. We show that this neutrino non-detection can provide valuable information about this gamma-ray burst's (GRB's) key physical parameters such as the emission radius R{sub d} , the bulk Lorentz factor {Gamma}, and the energy fraction converted into cosmic rays {epsilon}{sub p}. The results are discussed both in a model-independent way and in the specific scenarios of an internal shock (IS) model, a baryonic photospheric (BPH) model, and a magnetic photospheric (MPH) model. We find that the constraints are most stringent for the MPH model considered, but the constraints on the IS and the BPH models are fairly modest.

  2. VizieR Online Data Catalog: GRB prompt emission fitted with the DREAM model (Ahlgren+, 2015)

    Science.gov (United States)

    Ahlgren, B.; Larsson, J.; Nymark, T.; Ryde, F.; Pe'Er, A.

    2018-01-01

    We illustrate the application of the DREAM model by fitting it to two different, bright Fermi GRBs; GRB 090618 and GRB 100724B. While GRB 090618 is well fitted by a Band function, GRB 100724B was the first example of a burst with a significant additional BB component (Guiriec et al. 2011ApJ...727L..33G). GRB 090618 is analysed using Gamma-ray Burst Monitor (GBM) data (Meegan et al. 2009ApJ...702..791M) from the NaI and BGO detectors. For GRB 100724B, we used GBM data from the NaI and BGO detectors as well as Large Area Telescope Low Energy (LAT-LLE) data. For both bursts we selected NaI detectors seeing the GRB at an off-axis angle lower than 60° and the BGO detector as being the best aligned of the two BGO detectors. The spectra were fitted in the energy ranges 8-1000 keV (NaI), 200-40000 keV (BGO) and 30-1000 MeV (LAT-LLE). (2 data files).

  3. Deep Ly alpha imaging of two z=2.04 GRB host galaxy fields

    DEFF Research Database (Denmark)

    Fynbo, J.P.U.; Møller, Per; Thomsen, Bente

    2002-01-01

    We report on the results of deep narrow-band Lyalpha and broad-band U and I imaging of the fields of two Gamma-Ray bursts at redshift z = 2.04 (GRB 000301C and GRB 000926). We find that the host galaxy of GRB 000926 is an extended (more than 2 arcsec), strong Lyalpha emitter with a rest-frame equ......We report on the results of deep narrow-band Lyalpha and broad-band U and I imaging of the fields of two Gamma-Ray bursts at redshift z = 2.04 (GRB 000301C and GRB 000926). We find that the host galaxy of GRB 000926 is an extended (more than 2 arcsec), strong Lyalpha emitter with a rest...... - I colour than the eastern component, suggesting the presence of at least some dust. We do not detect the host galaxy of GRB 000301C in neither Lyalpha emission nor in U and I broad-band images. The strongest limit comes from combining the narrow and U-band imaging where we infer a limit of U...

  4. The large terminase DNA packaging motor grips DNA with its ATPase domain for cleavage by the flexible nuclease domain

    Science.gov (United States)

    Hilbert, Brendan J.; Hayes, Janelle A.; Stone, Nicholas P.; Xu, Rui-Gang

    2017-01-01

    Abstract Many viruses use a powerful terminase motor to pump their genome inside an empty procapsid shell during virus maturation. The large terminase (TerL) protein contains both enzymatic activities necessary for packaging in such viruses: the adenosine triphosphatase (ATPase) that powers DNA translocation and an endonuclease that cleaves the concatemeric genome at both initiation and completion of genome packaging. However, how TerL binds DNA during translocation and cleavage remains mysterious. Here we investigate DNA binding and cleavage using TerL from the thermophilic phage P74-26. We report the structure of the P74-26 TerL nuclease domain, which allows us to model DNA binding in the nuclease active site. We screened a large panel of TerL variants for defects in binding and DNA cleavage, revealing that the ATPase domain is the primary site for DNA binding, and is required for nuclease activity. The nuclease domain is dispensable for DNA binding but residues lining the active site guide DNA for cleavage. Kinetic analysis of DNA cleavage suggests flexible tethering of the nuclease domains during DNA cleavage. We propose that interactions with the procapsid during DNA translocation conformationally restrict the nuclease domain, inhibiting cleavage; TerL release from the capsid upon completion of packaging unlocks the nuclease domains to cleave DNA. PMID:28082398

  5. A tale of two GRB-SNe at a common redshift of ζ = 0.54

    International Nuclear Information System (INIS)

    Cano, Z.; Bersier, D.; Kobayashi, S.; Clay, N.; Mottram, C.; Mundell, C.G.; Small, E.; Smith, R.J.; Steele, I.; Guidorzi, C.; Curran, P.A.

    2011-01-01

    We present ground-based and Hubble Space Telescope optical observations of the optical transients (OTs) of long-duration Gamma Ray Bursts (GRBs) 060729 and 090618, both at a redshift of z=0.54. For GRB 060729, bumps are seen in the optical light curves (LCs), and the late-time broad-band spectral energy distributions (SEDs) of the OT resemble those of local Type Ic supernovae (SNe). For GRB 090618, the dense sampling of our optical observations has allowed us to detect well-defined bumps in the optical LCs, as well as a change in colour, that are indicative of light coming from a core-collapse SN. The accompanying SNe for both events are individually compared with SN1998bw, a known GRB supernova, and SN1994I, a typical Type Ic supernova without a known GRB counterpart, and in both cases the brightness and temporal evolution more closely resemble SN1998bw. We also exploit our extensive optical and radio data for GRB 090618, as well as the publicly available Swift-XRT data, and discuss the properties of the afterglow at early times. In the context of a simple jet-like model, the afterglow of GRB 090618 is best explained by the presence of a jet-break at t - t 0 ≥ 0.5 d. We then compare the rest-frame, peak V-band absolute magnitudes of all of the GRB and X-Ray Flash (XRF)-associated SNe with a large sample of local Type Ibc SNe, concluding that, when host extinction is considered, the peak magnitudes of the GRB/XRF-SNe cannot be distinguished from the peak magnitudes of non-GRB/XRF SNe. (authors)

  6. SWIFT GRB GRB071010B: OUTLIER OF THE E srcpeak - E γ AND E iso - E srcpeak - t srcjet CORRELATIONS

    International Nuclear Information System (INIS)

    Urata, Yuji; Lee, Induk; Ip, Wing Huen; Huang, Kuiyun; Im, Myungshin; Deng Jinsong; Liping Xin; Qiu Yulei; Wei Jianyan; Zheng Weikang; Krimm, Hans; Ohno, Masanori; Sugita, Satoshi; Tashiro, Makoto; Yamaoka, Kazutaka

    2009-01-01

    We present multi-band results for GRB071010B based on Swift, Suzaku, and ground-based optical observations. This burst is an ideal target to evaluate the robustness of the E src peak - E iso and E src peak - E γ relations, whose studies have been in stagnation due to the lack of the combined estimation of E src peak and long-term optical monitoring. The joint prompt spectral fitting using Swift/Burst Alert Telescope and Suzaku/Wide-band All-sky Monitor data yielded the spectral peak energy as E src peak of 86.5 +6.4 -6.3 keV and E iso of 2.25 +0.19 -0.16 x 10 52 erg with z = 0.947. The optical afterglow light curve is well fitted by a simple power law with temporal index α = -0.60 ± 0.02. The lower limit of temporal break in the optical light curve is 9.8 days. Our multi-wavelength analysis reveals that GRB071010B follows E src peak - E iso but violates the E src peak - E γ and E iso - E src peak - t src jet at more than the 3σ level.

  7. Calicivirus 3C-like proteinase inhibits cellular translation by cleavage of poly(A)-binding protein.

    Science.gov (United States)

    Kuyumcu-Martinez, Muge; Belliot, Gaël; Sosnovtsev, Stanislav V; Chang, Kyeong-Ok; Green, Kim Y; Lloyd, Richard E

    2004-08-01

    Caliciviruses are single-stranded RNA viruses that cause a wide range of diseases in both humans and animals, but little is known about the regulation of cellular translation during infection. We used two distinct calicivirus strains, MD145-12 (genus Norovirus) and feline calicivirus (FCV) (genus Vesivirus), to investigate potential strategies used by the caliciviruses to inhibit cellular translation. Recombinant 3C-like proteinases (r3CL(pro)) from norovirus and FCV were found to cleave poly(A)-binding protein (PABP) in the absence of other viral proteins. The norovirus r3CL(pro) PABP cleavage products were indistinguishable from those generated by poliovirus (PV) 3C(pro) cleavage, while the FCV r3CL(pro) products differed due to cleavage at an alternate cleavage site 24 amino acids downstream of one of the PV 3C(pro) cleavage sites. All cleavages by calicivirus or PV proteases separated the C-terminal domain of PABP that binds translation factors eIF4B and eRF3 from the N-terminal RNA-binding domain of PABP. The effect of PABP cleavage by the norovirus r3CL(pro) was analyzed in HeLa cell translation extracts, and the presence of r3CL(pro) inhibited translation of both endogenous and exogenous mRNAs. Translation inhibition was poly(A) dependent, and replenishment of the extracts with PABP restored translation. Analysis of FCV-infected feline kidney cells showed that the levels of de novo cellular protein synthesis decreased over time as virus-specific proteins accumulated, and cleavage of PABP occurred in virus-infected cells. Our data indicate that the calicivirus 3CL(pro), like PV 3C(pro), mediates the cleavage of PABP as part of its strategy to inhibit cellular translation. PABP cleavage may be a common mechanism among certain virus families to manipulate cellular translation.

  8. Caspase activation increases beta-amyloid generation independently of caspase cleavage of the beta-amyloid precursor protein (APP).

    Science.gov (United States)

    Tesco, Giuseppina; Koh, Young Ho; Tanzi, Rudolph E

    2003-11-14

    The amyloid precursor protein (APP) undergoes "alternative" proteolysis mediated by caspases. Three major caspase recognition sites have been identified in the APP, i.e. one at the C terminus (Asp720) and two at the N terminus (Asp197 and Asp219). Caspase cleavage at Asp720 has been suggested as leading to increased production of Abeta. Thus, we set out to determine which putative caspase sites in APP, if any, are cleaved in Chinese hamster ovary cell lines concurrently with the increased Abeta production that occurs during apoptosis. We found that cleavage at Asp720 occurred concurrently with caspase 3 activation and the increased production of total secreted Abeta and Abeta1-42 in association with staurosporine- and etoposide-induced apoptosis. To investigate the contribution of caspase cleavage of APP to Abeta generation, we expressed an APP mutant truncated at Asp720 that mimics APP caspase cleavage at the C-terminal site. This did not increase Abeta generation but, in contrast, dramatically decreased Abeta production in Chinese hamster ovary cells. Furthermore, the ablation of caspase-dependent cleavage at Asp720, Asp197, and Asp219 (by site-directed mutagenesis) did not prevent enhanced Abeta production following etoposide-induced apoptosis. These findings indicate that the enhanced Abeta generation associated with apoptosis does not require cleavage of APP at its C-terminal (Asp720) and/or N-terminal caspase sites.

  9. Relativistic Hydrodynamics and Spectral Evolution of GRB Jets

    Science.gov (United States)

    Cuesta-Martínez, C.

    2017-09-01

    In this thesis we study the progenitor systems of long gamma-ray bursts (GRBs) using numerical models of their dynamics and the electromagnetic emission. Of all the possible classes of events, we focus on those showing a prominent component of thermal emission, which might be generated due to the interaction of a relativistic jet with the medium into which it is propagating. The main part of the thesis is devoted to modelling GRBs from two different clases of progenitors: ultra-long GRBs dominated by blackbody emission and GRBs associated with core-collapse supernovae (SNe). The study of GRB jets and their radiative emission has been basically divided into two steps. First, the dynamical evolution of relativistic jets can be simulated by means of multidimensional special relativistic hydrodynamic simulations which have been performed with the MRGENESIS code. Second, the synthetic emission from such jets is computed with the relativistic radiative transfer code SPEV in a post-processing stage assuming different radiative processes in which we follow the temporal and spectral evolution of the emitted radiation. An instrumental part of this project consisted in extending SPEV to include thermal processes, such as thermal bremsstrahlung, in order to account for the thermal signal that may arise in some GRBs. In the first part of this thesis, we extend an existing theoretical model to explain the class of blackbody-dominated GRBs (BBD-GRBs), i.e., long lasting events characterized by the presence of a notable thermal component trailing the GRB prompt emission, and a rather weak traditional afterglow. GRB 101225A, the "Christmas burst", is the most prominent member of this class. It has been suggested that BBD-GRBs could result from the merger of a binary system formed by a neutron star and the Helium core of an evolved, massive star. We model in 2D the propagation of ultrarelativistic jets through the environments created by such mergers. We outline the most relevant

  10. Cleavage specificity analysis of six type II transmembrane serine proteases (TTSPs using PICS with proteome-derived peptide libraries.

    Directory of Open Access Journals (Sweden)

    Olivier Barré

    Full Text Available Type II transmembrane serine proteases (TTSPs are a family of cell membrane tethered serine proteases with unclear roles as their cleavage site specificities and substrate degradomes have not been fully elucidated. Indeed just 52 cleavage sites are annotated in MEROPS, the database of proteases, their substrates and inhibitors.To profile the active site specificities of the TTSPs, we applied Proteomic Identification of protease Cleavage Sites (PICS. Human proteome-derived database searchable peptide libraries were assayed with six human TTSPs (matriptase, matriptase-2, matriptase-3, HAT, DESC and hepsin to simultaneously determine sequence preferences on the N-terminal non-prime (P and C-terminal prime (P' sides of the scissile bond. Prime-side cleavage products were isolated following biotinylation and identified by tandem mass spectrometry. The corresponding non-prime side sequences were derived from human proteome databases using bioinformatics. Sequencing of 2,405 individual cleaved peptides allowed for the development of the family consensus protease cleavage site specificity revealing a strong specificity for arginine in the P1 position and surprisingly a lysine in P1' position. TTSP cleavage between R↓K was confirmed using synthetic peptides. By parsing through known substrates and known structures of TTSP catalytic domains, and by modeling the remainder, structural explanations for this strong specificity were derived.Degradomics analysis of 2,405 cleavage sites revealed a similar and characteristic TTSP family specificity at the P1 and P1' positions for arginine and lysine in unfolded peptides. The prime side is important for cleavage specificity, thus making these proteases unusual within the tryptic-enzyme class that generally has overriding non-prime side specificity.

  11. Yeast ribonuclease III uses a network of multiple hydrogen bonds for RNA binding and cleavage.

    Science.gov (United States)

    Lavoie, Mathieu; Abou Elela, Sherif

    2008-08-19

    Members of the bacterial RNase III family recognize a variety of short structured RNAs with few common features. It is not clear how this group of enzymes supports high cleavage fidelity while maintaining a broad base of substrates. Here we show that the yeast orthologue of RNase III (Rnt1p) uses a network of 2'-OH-dependent interactions to recognize substrates with different structures. We designed a series of bipartite substrates permitting the distinction between binding and cleavage defects. Each substrate was engineered to carry a single or multiple 2'- O-methyl or 2'-fluoro ribonucleotide substitutions to prevent the formation of hydrogen bonds with a specific nucleotide or group of nucleotides. Interestingly, introduction of 2'- O-methyl ribonucleotides near the cleavage site increased the rate of catalysis, indicating that 2'-OH are not required for cleavage. Substitution of nucleotides in known Rnt1p binding site with 2'- O-methyl ribonucleotides inhibited cleavage while single 2'-fluoro ribonucleotide substitutions did not. This indicates that while no single 2'-OH is essential for Rnt1p cleavage, small changes in the substrate structure are not tolerated. Strikingly, several nucleotide substitutions greatly increased the substrate dissociation constant with little or no effect on the Michaelis-Menten constant or rate of catalysis. Together, the results indicate that Rnt1p uses a network of nucleotide interactions to identify its substrate and support two distinct modes of binding. One mode is primarily mediated by the dsRNA binding domain and leads to the formation of stable RNA/protein complex, while the other requires the presence of the nuclease and N-terminal domains and leads to RNA cleavage.

  12. Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2

    International Nuclear Information System (INIS)

    Ivancic, Monika; Daly, Roger J.; Lyons, Barbara A.

    2003-01-01

    The solution structure of the hGrb7-SH2 domain in complex with a ten amino acid phosphorylated peptide ligand representative of the erbB2 receptor tyrosine kinase (pY1139) is presented as determined by nuclear magnetic resonance methods. The hGrb7-SH2 domain structure reveals the Src homology 2 domain topology consisting of a central β-sheet capped at each end by an α-helix. The presence of a four residue insertion in the region between β-strand E and the EF loop and resulting influences on the SH2 domain/peptide complex structure are discussed. The binding conformation of the erbB2 peptide is in a β-turn similar to that found in phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our knowledge this is only the second example of an SH2 domain binding its naturally occurring ligands in a turn, instead of extended, conformation. Close contacts between residues responsible for binding specificity in hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect of mutation of these residues on the hGrb7-SH2 domain structure is discussed

  13. Modeling the Multiband Afterglows of GRB 060614 and GRB 060908: Further Evidence for a Double Power-law Hard Electron Energy Spectrum

    Science.gov (United States)

    Zhang, Q.; Xiong, S. L.; Song, L. M.

    2018-04-01

    Electrons accelerated in relativistic collisionless shocks are usually assumed to follow a power-law energy distribution with an index of p. Observationally, although most gamma-ray bursts (GRBs) have afterglows that are consistent with p > 2, there are still a few GRBs suggestive of a hard (p law hard electron energy (DPLH) spectrum with 1 2 and an “injection break” assumed as γ b ∝ γ q in the highly relativistic regime, where γ is the bulk Lorentz factor of the jet. In this paper, we show that GRB 060614 and GRB 060908 provide further evidence for such a DPLH spectrum. We interpret the multiband afterglow of GRB 060614 with the DPLH model in a homogeneous interstellar medium by taking into account a continuous energy injection process, while, for GRB 060908, a wind-like circumburst density profile is used. The two bursts, along with GRB 091127, suggest a similar behavior in the evolution of the injection break, with q ∼ 0.5. Whether this represents a universal law of the injection break remains uncertain and more afterglow observations such as these are needed to test this conjecture.

  14. REM observations of GRB060418 and GRB060607A: the onset of the afterglow and the initial fireball Lorentz factor determination

    Energy Technology Data Exchange (ETDEWEB)

    Molinari, E.; Covino, S.; D' Avanzo, P.; Chincarini, G.; Zerbi, F.M.; Conconi, P.; Malaspina, G.; Campana, S.; Rizzuto, D.; Tagliaferri, G. [Osserv Astron Brera, INAF, I-23807 Merate, LC, (Italy); Vergani, S.D.; Meurs, E.J.A.; Ward, P.A. [DIAS, Dunsink Observ, Dublin 15, (Ireland); Vergani, S.D.; Norci, L. [Dublin City Univ, Sch Phys Sci, NCPST, Dublin 9, (Ireland); Malesani, D. [SISSA, ISAS, I-34014 Trieste, (Italy); Malesani, D. [Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen, (Denmark); D' Avanzo, P. [Univ Insubria, Dipartimento Matemat and Fis, I-22100 Como, (Italy); Chincarini, G.; Rizzuto, D. [Univ Milan, I-20126 Milan, (Italy); Antonelli, L.A.; Testa, V.; Vitali, F.; D' Alessio, F.; Guetta, D.; Piranomonte, S.; Stella, L. [Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, (Italy); Tosti, G. [Univ Perugia, Dipartimento Fis, Osservatorio Astron, I-06123 Perugia, (Italy); Nicastro, L.; Palazzi, E.; Masetti, N. [IASF Bologna, INAF, I-40129 Bologna, (Italy); Goldoni, P. [APC, Lab Astroparticule and Cosmol, UMR 7164, F-75231 Paris 05, (France); Goldoni, P. [CEA Saclay, DSM, DAPNIA, Serv Astrophys, F-91191 Gif Sur Yvette, (France)] (and others)

    2007-07-01

    Context. Gamma-ray burst (GRB) emission is believed to originate in highly relativistic fireballs. Aims. Currently, only lower limits were securely set to the initial fireball Lorentz factor {gamma}{sub 0}. We aim to provide a direct measure of {gamma}{sub 0}. Methods. The early-time afterglow light curve carries information about {gamma}{sub 0}, which determines the time of the afterglow peak. We have obtained early observations of the near-infrared afterglows of GRB060418 and GRB060607A with the REM robotic telescope. Results. For both events, the afterglow peak could be clearly singled out, allowing a firm determination of the fireball Lorentz of {gamma}{sub 0} similar to 400, fully confirming the highly relativistic nature of GRB fireballs. The deceleration radius was inferred to be R-dec approximate to 10{sup 17} cm. This is much larger than the internal shocks radius (believed to power the prompt emission), thus providing further evidence for a different origin of the prompt and afterglow stages of the GRB. (authors)

  15. Spectro-photometric study of the GRB 030329 host galaxy

    International Nuclear Information System (INIS)

    Gorosabel, J.; Ramirez, D. Perez

    2005-01-01

    In this study we present optical/near-infrared (NIR) broad band photometry and optical spectroscopic observations of the GRB 030329 host galaxy. The Spectral Energy Distribution (SED) of the host is consistent with a starburst galaxy template with a dominant stellar population age of ∼ 150 Myr and an extinction A ν ∼ 0.6. Analysis of the spectral emission lines shows that the host is likely a low metallicity galaxy. Two independent diagnostics, based on the restframe UV continuum and the [OII] line flux, provide a consistent unextincted star formation rate of SFRN ∼ 0.6 Myr -1 . The low absolute magnitude of the host (M B ∼ -16.5) implies a high specific star formation rate value, SSFR ≅ 34 Myr -1 (L/L) -1

  16. Ten per cent polarized optical emission from GRB 090102.

    Science.gov (United States)

    Steele, I A; Mundell, C G; Smith, R J; Kobayashi, S; Guidorzi, C

    2009-12-10

    The nature of the jets and the role of magnetic fields in gamma-ray bursts (GRBs) remains unclear. In a baryon-dominated jet only weak, tangled fields generated in situ through shocks would be present. In an alternative model, jets are threaded with large-scale magnetic fields that originate at the central engine and that accelerate and collimate the material. To distinguish between the models the degree of polarization in early-time emission must be measured; however, previous claims of gamma-ray polarization have been controversial. Here we report that the early optical emission from GRB 090102 was polarized at 10 +/- 1 per cent, indicating the presence of large-scale fields originating in the expanding fireball. If the degree of polarization and its position angle were variable on timescales shorter than our 60-second exposure, then the peak polarization may have been larger than ten per cent.

  17. A central role for GRB10 in regulation of islet function in man.

    Directory of Open Access Journals (Sweden)

    Inga Prokopenko

    2014-04-01

    Full Text Available Variants in the growth factor receptor-bound protein 10 (GRB10 gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.

  18. Radioactive decay of the late-time light curves of GRB-SNe

    Science.gov (United States)

    Misra, Kuntal; Fruchte, Andrew Steven

    2018-04-01

    We present the late-time Hubble Space Telescope observations of two GRB associated supernovae, GRB 030329/SN 2003dh and XRF 060218/SN 2006aj. Using the multi-color data upto ˜ 320 days after the burst, we constrain the late-time decay nature of these supernovae. The decay rates of SN 2003dh are steeper than SN 2006aj. A comparison with two other GRB supernovae, GRB 980425/SN 1998bw and the supernova associated with XRF 020903, shows that the decay rates of SN 2003dh are similar to XRF 020903 and those of SN 2006aj are similar to SN 1998bw. The late-time decay rates are steeper than the 56Co?56Fe radioactive decay rate (0.0098 mag day-1) indicating that there is some leakage of gamma-rays.

  19. FERMI OBSERVATIONS OF HIGH-ENERGY GAMMA-RAY EMISSION FROM GRB 080825C

    International Nuclear Information System (INIS)

    Abdo, A. A.; Ackermann, M.; Bechtol, K.; Berenji, B.; Bloom, E. D.; Borgland, A. W.; Bouvier, A.; Asano, K.; Atwood, W. B.; Axelsson, M.; Baldini, L.; Bellazzini, R.; Bregeon, J.; Ballet, J.; Band, D. L.; Barbiellini, G.; Bastieri, D.; Bhat, P. N.; Bissaldi, E.; Bonamente, E.

    2009-01-01

    The Fermi Gamma-ray Space Telescope has opened a new high-energy window in the study of gamma-ray bursts (GRBs). Here we present a thorough analysis of GRB 080825C, which triggered the Fermi Gamma-ray Burst Monitor (GBM), and was the first firm detection of a GRB by the Fermi Large Area Telescope (LAT). We discuss the LAT event selections, background estimation, significance calculations, and localization for Fermi GRBs in general and GRB 080825C in particular. We show the results of temporal and time-resolved spectral analysis of the GBM and LAT data. We also present some theoretical interpretation of GRB 080825C observations as well as some common features observed in other LAT GRBs.

  20. Monoclonal antibodies to the reactive centre loop (RCL) of human corticosteroid-binding globulin (CBG) can protect against proteolytic cleavage.

    Science.gov (United States)

    Lewis, John G; Elder, Peter A

    2017-07-01

    Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation and is a non-functional member of the family of serine protease inhibitors (serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL can be cleaved by human neutrophil elastase, released from activated neutrophils, and can also be cleaved at nearby site(s) by elastase released by Pseudomonas aeruginosa, and at two further sites, also within the RCL, by bovine chymotrypsin. Cleavage of the RCL results in a conformational change accompanied by a marked decrease in affinity for cortisol and hence its release at the site of proteolysis. These cleavages are irreversible and the similar half-lives of cleaved and intact CBG could mean that there may be some advantage in slowing the rate of CBG cleavage in acute inflammation thereby increasing the proportion of intact CBG in circulation. Here we show, for the first time, that pre-incubation of tethered human CBG with two monoclonal antibodies to the RCL of CBG protects against cleavage by all three enzymes. Furthermore, in plasma, pre-incubation with both RCL monoclonal antibodies delays neutrophil elastase cleavage of the RCL and one of these RCL monoclonal antibodies also delays bovine chymotrypsin cleavage of the RCL. These findings may provide a basis and rationale for the concept of the use of RCL antibodies as therapeutic agents to effectively increase the proportion of intact CBG in circulation which may be of benefit in acute inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target.

    Science.gov (United States)

    Watson, Gabrielle M; Lucas, William A H; Gunzburg, Menachem J; Wilce, Jacqueline A

    2017-01-01

    Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine), however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors.

  2. Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target

    Directory of Open Access Journals (Sweden)

    Gabrielle M. Watson

    2017-09-01

    Full Text Available Growth factor receptor bound protein 7 (Grb7 is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine, however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors.

  3. Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target

    Science.gov (United States)

    Watson, Gabrielle M.; Lucas, William A. H.; Gunzburg, Menachem J.; Wilce, Jacqueline A.

    2017-01-01

    Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine), however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors. PMID:29018805

  4. A Decade of GRB Follow-Up by BOOTES in Spain (2003–2013

    Directory of Open Access Journals (Sweden)

    Martin Jelínek

    2016-01-01

    Full Text Available This article covers ten years of GRB follow-ups by the Spanish BOOTES stations: 71 follow-ups providing 23 detections. Follow-ups by BOOTES-1B from 2005 to 2008 were given in a previous article and are here reviewed and updated, and additional detection data points are included as the former article merely stated their existence. The all-sky cameras CASSANDRA have not yet detected any GRB optical afterglows, but limits are reported where available.

  5. Structural basis for the interaction of the adaptor protein grb14 with activated ras.

    Directory of Open Access Journals (Sweden)

    Rohini Qamra

    Full Text Available Grb14, a member of the Grb7-10-14 family of cytoplasmic adaptor proteins, is a tissue-specific negative regulator of insulin signaling. Grb7-10-14 contain several signaling modules, including a Ras-associating (RA domain, a pleckstrin-homology (PH domain, a family-specific BPS (between PH and SH2 region, and a C-terminal Src-homology-2 (SH2 domain. We showed previously that the RA and PH domains, along with the BPS region and SH2 domain, are necessary for downregulation of insulin signaling. Here, we report the crystal structure at 2.4-Å resolution of the Grb14 RA and PH domains in complex with GTP-loaded H-Ras (G12V. The structure reveals that the Grb14 RA and PH domains form an integrated structural unit capable of binding simultaneously to small GTPases and phosphoinositide lipids. The overall mode of binding of the Grb14 RA domain to activated H-Ras is similar to that of the RA domains of RalGDS and Raf1 but with important distinctions. The integrated RA-PH structural unit in Grb7-10-14 is also found in a second adaptor family that includes Rap1-interacting adaptor molecule (RIAM and lamellipodin, proteins involved in actin-cytoskeleton rearrangement. The structure of Grb14 RA-PH in complex with H-Ras represents the first detailed molecular characterization of tandem RA-PH domains bound to a small GTPase and provides insights into the molecular basis for specificity.

  6. Predicting proteasomal cleavage sites: a comparison of available methods

    DEFF Research Database (Denmark)

    Saxova, P.; Buus, S.; Brunak, Søren

    2003-01-01

    -terminal, in particular, of CTL epitopes is cleaved precisely by the proteasome, whereas the N-terminal is produced with an extension, and later trimmed by peptidases in the cytoplasm and in the endoplasmic reticulum. Recently, three publicly available methods have been developed for prediction of the specificity...

  7. A PHOTOMETRIC REDSHIFT OF z ∼ 9.4 FOR GRB 090429B

    International Nuclear Information System (INIS)

    Cucchiara, A.; Fox, D. B.; Wu, X. F.; Toma, K.; Levan, A. J.; Tanvir, N. R.; Rowlinson, A.; Ukwatta, T. N.; Berger, E.; Kruehler, T.; Greiner, J.; Olivares, F. E.; Yoldas, A. Kuepcue; Amati, L.; Sakamoto, T.; Roth, K.; Stephens, A.; Fritz, Alexander; Fynbo, J. P. U.; Hjorth, J.

    2011-01-01

    Gamma-ray bursts (GRBs) serve as powerful probes of the early universe, with their luminous afterglows revealing the locations and physical properties of star-forming galaxies at the highest redshifts, and potentially locating first-generation (Population III) stars. Since GRB afterglows have intrinsically very simple spectra, they allow robust redshifts from low signal-to-noise spectroscopy, or photometry. Here we present a photometric redshift of z ∼ 9.4 for the Swift detected GRB 090429B based on deep observations with Gemini-North, the Very Large Telescope, and the GRB Optical and Near-infrared Detector. Assuming a Small Magellanic Cloud dust law (which has been found in a majority of GRB sight lines), the 90% likelihood range for the redshift is 9.06 7. The non-detection of the host galaxy to deep limits (Y(AB) ∼ 28, which would correspond roughly to 0.001L* at z = 1) in our late-time optical and infrared observations with the Hubble Space Telescope strongly supports the extreme-redshift origin of GRB 090429B, since we would expect to have detected any low-z galaxy, even if it were highly dusty. Finally, the energetics of GRB 090429B are comparable to those of other GRBs and suggest that its progenitor is not greatly different from those of lower redshift bursts.

  8. Fusion protein based on Grb2-SH2 domain for cancer therapy

    International Nuclear Information System (INIS)

    Saito, Yuriko; Furukawa, Takako; Arano, Yasushi; Fujibayashi, Yasuhisa; Saga, Tsuneo

    2010-01-01

    Research highlights: → Grb2 mediates EGFR signaling through binding to phosphorylate EGFR with SH2 domain. → We generated fusion proteins containing 1 or 2 SH2 domains of Grb2 added with TAT. → The one with 2 SH2 domains (TSSF) interfered ERK phosphorylation. → TSSF significantly delayed the growth of EGFR overexpressing tumor in a mouse model. -- Abstract: Epidermal growth factor receptor (EGFR) is one of the very attractive targets for cancer therapy. In this study, we generated fusion proteins containing one or two Src-homology 2 (SH2) domains of growth factor receptor bound protein 2 (Grb2), which bind to phosphorylated EGFR, added with HIV-1 transactivating transcription for cell membrane penetration (termed TSF and TSSF, respectively). We examined if they can interfere Grb2-mediated signaling pathway and suppress tumor growth as expected from the lack of SH3 domain, which is necessary to intermediate EGFR-Grb2 cell signaling, in the fusion proteins. The transduction efficiency of TSSF was similar to that of TSF, but the binding activity of TSSF to EGFR was higher than that of TSF. Treatment of EGFR-overexpressing cells showed that TSSF decreased p42-ERK phosphorylation, while TSF did not. Both the proteins delayed cell growth but did not induce cell death in culture. TSSF also significantly suppressed tumor growth in vivo under consecutive administration. In conclusion, TSSF showed an ability to inhibit EGFR-Grb2 signaling and could have a potential to treat EGFR-activated cancer.

  9. A MISSING-LINK IN THE SUPERNOVA–GRB CONNECTION: THE CASE OF SN 2012ap

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborti, Sayan; Soderberg, Alicia; Kamble, Atish; Margutti, Raffaella; Milisavljevic, Dan; Dittmann, Jason [Institute for Theory and Computation, Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Chomiuk, Laura [Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824 (United States); Yadav, Naveen; Ray, Alak [Tata Institute of Fundamental Research, 1 Homi Bhabha Road, Mumbai 400005 (India); Hurley, Kevin [Space Sciences Laboratory, University of California, 7 Gauss Way, Berkeley, CA 94720 (United States); Bietenholz, Michael [Department of Physics and Astronomy, York University, 4700 Keele St., M3J 1P3 Ontario (Canada); Brunthaler, Andreas [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Pignata, Giuliano [Departamento de Ciencias Fisicas, Universidad Andres Bello, Avda. Republica 252, Santiago (Chile); Pian, Elena [Scuola Normale Superiore, Piazza Dei Cavalieri 7—I-56126 Pisa (Italy); Mazzali, Paolo [Liverpool John Moores University, IC2, 146 Brownlow Hill, Liverpool (United Kingdom); Fransson, Claes [Department of Astronomy, Stockholm University, AlbaNova, SE-106 91 Stockholm (Sweden); Bartel, Norbert [Hartebeesthoek Radio Astronomy Observatory, PO Box 443, Krugersdrop, 1740 (South Africa); Hamuy, Mario [Departamento de Astronoma, Universidad de Chile (Chile); Levesque, Emily [University of Colorado, C327A, Boulder, CO 80309 (United States); MacFadyen, Andrew, E-mail: schakraborti@fas.harvard.edu [New York University, 4 Washington Place, New York, NY 10003 (United States); and others

    2015-06-01

    Gamma-ray bursts (GRBs) are characterized by ultra-relativistic outflows, while supernovae are generally characterized by non-relativistic ejecta. GRB afterglows decelerate rapidly, usually within days, because their low-mass ejecta rapidly sweep up a comparatively larger mass of circumstellar material. However, supernovae with heavy ejecta can be in nearly free expansion for centuries. Supernovae were thought to have non-relativistic outflows except for a few relativistic ones accompanied by GRBs. This clear division was blurred by SN 2009bb, the first supernova with a relativistic outflow without an observed GRB. However, the ejecta from SN 2009bb was baryon loaded and in nearly free expansion for a year, unlike GRBs. We report the first supernova discovered without a GRB but with rapidly decelerating mildly relativistic ejecta, SN 2012ap. We discovered a bright and rapidly evolving radio counterpart driven by the circumstellar interaction of the relativistic ejecta. However, we did not find any coincident GRB with an isotropic fluence of more than one-sixth of the fluence from GRB 980425. This shows for the first time that central engines in SNe Ic, even without an observed GRB, can produce both relativistic and rapidly decelerating outflows like GRBs.

  10. A MISSING-LINK IN THE SUPERNOVA–GRB CONNECTION: THE CASE OF SN 2012ap

    International Nuclear Information System (INIS)

    Chakraborti, Sayan; Soderberg, Alicia; Kamble, Atish; Margutti, Raffaella; Milisavljevic, Dan; Dittmann, Jason; Chomiuk, Laura; Yadav, Naveen; Ray, Alak; Hurley, Kevin; Bietenholz, Michael; Brunthaler, Andreas; Pignata, Giuliano; Pian, Elena; Mazzali, Paolo; Fransson, Claes; Bartel, Norbert; Hamuy, Mario; Levesque, Emily; MacFadyen, Andrew

    2015-01-01

    Gamma-ray bursts (GRBs) are characterized by ultra-relativistic outflows, while supernovae are generally characterized by non-relativistic ejecta. GRB afterglows decelerate rapidly, usually within days, because their low-mass ejecta rapidly sweep up a comparatively larger mass of circumstellar material. However, supernovae with heavy ejecta can be in nearly free expansion for centuries. Supernovae were thought to have non-relativistic outflows except for a few relativistic ones accompanied by GRBs. This clear division was blurred by SN 2009bb, the first supernova with a relativistic outflow without an observed GRB. However, the ejecta from SN 2009bb was baryon loaded and in nearly free expansion for a year, unlike GRBs. We report the first supernova discovered without a GRB but with rapidly decelerating mildly relativistic ejecta, SN 2012ap. We discovered a bright and rapidly evolving radio counterpart driven by the circumstellar interaction of the relativistic ejecta. However, we did not find any coincident GRB with an isotropic fluence of more than one-sixth of the fluence from GRB 980425. This shows for the first time that central engines in SNe Ic, even without an observed GRB, can produce both relativistic and rapidly decelerating outflows like GRBs

  11. Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)

    DEFF Research Database (Denmark)

    Huebner, K; Kastury, K; Druck, T

    1994-01-01

    "adapter" proteins, which are involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as ras, because adaptor protein genes could also, logically, serve as targets of mutation, rearrangement, or other aberration in disease. Therefore, DNAs from panels of rodent-human......Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and humans. Thus, it can be important to determine chromosomal map positions of genes encoding...... hybrids carrying defined complements of human chromosomes were assayed for the presence of the cognate genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src homology 2 and 3) domain-containing adapter proteins. Additionally, NCK and SHC genes were more narrowly localized by chromosomal in situ...

  12. Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy.

    Science.gov (United States)

    Dharmawardana, Pathirage G; Peruzzi, Benedetta; Giubellino, Alessio; Burke, Terrence R; Bottaro, Donald P

    2006-01-01

    Growth factor receptor-bound 2 (Grb2) is a ubiquitously expressed adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. As such, it has been implicated in the oncogenesis of several important human malignancies. In addition to this function, research over the last decade has revealed other fundamental roles for Grb2 in cell motility and angiogenesis--processes that also contribute to tumor growth, invasiveness and metastasis. This functional profile makes Grb2 a high priority target for anti-cancer drug development. Knowledge of Grb2 protein structure, its component Src homology domains and their respective structure-function relationships has facilitated the rapid development of sophisticated drug candidates that can penetrate cells, bind Grb2 with high affinity and potently antagonize Grb2 signaling. These novel compounds offer considerable promise in our growing arsenal of rationally designed anti-cancer therapeutics.

  13. [Cleavage of DNA fragments induced by UV nanosecond laser excitation at 193 nm].

    Science.gov (United States)

    Vtiurina, N N; Grokhovskiĭ, S L; Filimonov, I V; Medvedkov, O I; Nechipurenko, D Iu; Vasil'ev, S A; Nechipurenko, Iu D

    2011-01-01

    The cleavage of dsDNA fragments in aqueous solution after irradiation with UV laser pulses at 193 nm has been studied. Samples were investigated using polyacrylamide gel electrophoresis. The intensity of damage of particular phosphodiester bond after hot alkali treatment was shown to depend on the base pair sequence. It was established that the probability of cleavage is twice higher for sites of DNA containing two or more successively running guanine residues. A possible mechanism of damage to the DNA molecule connected with the migration of holes along the helix is discussed.

  14. Stimulation of topoisomerase II mediated DNA cleavage at specific sequence elements by the 2-nitroimidazole Ro 15-0216

    International Nuclear Information System (INIS)

    Sorensen, B.S.; Jensen, P.S.; Andersen, A.H.; Christiansen, K.; Alsner, J.; Thomsen, B.; Westergaard, O.

    1990-01-01

    The effect of the 2-nitroimidazole Ro 15-0216 upon the interaction between purified topoisomerase II and its DNA substrate was investigated. The cleavage reaction in the presence of this DNA-nonintercalative drug took place with the hallmarks of a regular topoisomerase II mediated cleavage reaction, including covalent linkage of the enzyme to the cleaved DNA. In the presence of Ro 15-0216, topoisomerase II mediated cleavage was extensively stimulated at major cleavage sites of which only one existed in the 4363 base pair pBR322 molecule. The sites stimulated by Ro 15-0216 shared a pronounced sequence homology, indicating that a specific nucleotide sequence is crucial for the action of this drug. The effect of Ro 15-0216 thus differs from that of the clinically important topoisomerase II targeted agents such as mAMSA, VM26, and VP16, which enhance enzyme-mediated cleavage at a multiple number of sites. In contrast to the previous described drugs, Ro 15-0216 did not exert any inhibitory effect on the enzyme's catalytic activity. This observation might be ascribed to the low stability of the cleavage complexes formed in the presence of Ro 15-0216 as compared to the stability of the ones formed in the presence of traditional topoisomerase II targeted drugs

  15. VLT identification of the optical afterglow of the gamma-ray burst GRB000131 at z=4.50

    DEFF Research Database (Denmark)

    Andersen, M.I.; Hjorth, J.; Jesen, B.L.

    2000-01-01

    We report the discovery of the gamma-ray burst GRB 000131 and its optical afterglow. The optical identification was made with the VLT 84 hours after the burst following a BATSE detection and an Inter Planetary Network localization. GRB 000131 was a bright, long-duration GRB, with an apparent...... Angstrom. This places GRB 000131 at a redshift of 4.500 +/- 0.015. The inferred isotropic energy release in gamma rays alone was similar to 10(54) erg (depending on the assumed cosmology). The rapid power-law decay of the afterglow (index alpha = 2.25, similar to bursts with a prior break in the lightcurve...

  16. VLT identification of the optical afterglow of the gamma-ray burst GRB 000131 at z=4.50

    DEFF Research Database (Denmark)

    Andersen, M.I.; Hjorth, J.; Pedersen, H.

    2000-01-01

    We report the discovery of the gamma-ray burst GRB 000131 and its optical afterglow. The optical identification was made with the VLT 84 hours after the burst following a BATSE detection and an Inter Planetary Network localization. GRB 000131 was a bright, long-duration GRB, with an apparent...... Angstrom. This places GRB 000131 at a redshift of 4.500 +/- 0.015. The inferred isotropic energy release in gamma rays alone was similar to 10(54) erg (depending on the assumed cosmology). The rapid power-law decay of the afterglow (index alpha = 2.25, similar to bursts with a prior break in the lightcurve...

  17. Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7.

    Science.gov (United States)

    Pandey, A; Liu, X; Dixon, J E; Di Fiore, P P; Dixit, V M

    1996-05-03

    Adapter proteins containing Src homology 2 (SH2) domains link transmembrane receptor protein-tyrosine kinases to downstream signal transducing molecules. A family of SH2 containing adapter proteins including Grb7 and Grb10 has been recently identified. We had previously shown that Grb10 associates with Ret via its SH2 domain in an activation-dependent manner (Pandey, A., Duan, H., Di Fiore, P.P., and Dixit, V.M. (1995) J. Biol, Chem. 270, 21461-21463). We now demonstrate that the related adapter molecule Grb7 also associates with Ret in vitro and in vivo, and that the binding of the SH2 domain of Grb7 to Ret is direct. This binding is dependent upon Ret autophosphorylation since Grb7 is incapable of binding a kinase-defective mutant of Ret. Thus two members of the Grb family, Grb7 and Grb10, likely relay signals emanating from Ret to other, as yet, unidentified targets within the cell.

  18. Controllable laser thermal cleavage of sapphire wafers

    Science.gov (United States)

    Xu, Jiayu; Hu, Hong; Zhuang, Changhui; Ma, Guodong; Han, Junlong; Lei, Yulin

    2018-03-01

    Laser processing of substrates for light-emitting diodes (LEDs) offers advantages over other processing techniques and is therefore an active research area in both industrial and academic sectors. The processing of sapphire wafers is problematic because sapphire is a hard and brittle material. Semiconductor laser scribing processing suffers certain disadvantages that have yet to be overcome, thereby necessitating further investigation. In this work, a platform for controllable laser thermal cleavage was constructed. A sapphire LED wafer was modeled using the finite element method to simulate the thermal and stress distributions under different conditions. A guide groove cut by laser ablation before the cleavage process was observed to guide the crack extension and avoid deviation. The surface and cross section of sapphire wafers processed using controllable laser thermal cleavage were characterized by scanning electron microscopy and optical microscopy, and their morphology was compared to that of wafers processed using stealth dicing. The differences in luminous efficiency between substrates prepared using these two processing methods are explained.

  19. Pressure modulates the self-cleavage step of the hairpin ribozyme

    Science.gov (United States)

    Schuabb, Caroline; Kumar, Narendra; Pataraia, Salome; Marx, Dominik; Winter, Roland

    2017-03-01

    The ability of certain RNAs, denoted as ribozymes, to not only store genetic information but also catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth. This, however, might have evolved under extreme environmental conditions, including the deep sea with pressures in the kbar regime. Here we study pressure-induced effects on the self-cleavage of hairpin ribozyme by following structural changes in real-time. Our results suggest that compression of the ribozyme leads to an accelerated transesterification reaction, being the self-cleavage step, although the overall process is retarded in the high-pressure regime. The results reveal that favourable interactions between the reaction site and neighbouring nucleobases are strengthened under pressure, resulting therefore in an accelerated self-cleavage step upon compression. These results suggest that properly engineered ribozymes may also act as piezophilic biocatalysts in addition to their hitherto known properties.

  20. Fetal hemoglobin is much less prone to DNA cleavage compared to the adult protein

    Directory of Open Access Journals (Sweden)

    Sandeep Chakane

    2017-08-01

    Full Text Available Hemoglobin (Hb is well protected inside the red blood cells (RBCs. Upon hemolysis and when free in circulation, Hb can be involved in a range of radical generating reactions and may thereby attack several different biomolecules. In this study, we have examined the potential damaging effects of cell-free Hb on plasmid DNA (pDNA. Hb induced cleavage of supercoiled pDNA (sc pDNA which was proportional to the concentration of Hb applied. Almost 70% of sc pDNA was converted to open circular or linear DNA using 10 µM of Hb in 12 h. Hb can be present in several different forms. The oxy (HbO2 and met forms are most reactive, while the carboxy-protein shows only low hydrolytic activity. Hemoglobin A (HbA could easily induce complete pDNA cleavage while fetal hemoglobin (HbF was three-fold less reactive. By inserting, a redox active cysteine residue on the surface of the alpha chain of HbF by site-directed mutagenesis, the DNA cleavage reaction was enhanced by 82%. Reactive oxygen species were not directly involved in the reaction since addition of superoxide dismutase and catalase did not prevent pDNA cleavage. The reactivity of Hb with pDNA can rather be associated with the formation of protein based radicals. Keywords: Adult hemoglobin, Fetal hemoglobin, Supercoiled plasmid DNA, DNA cleavage, Cysteine, Protein radicals

  1. CONSTRAINING THE GRB-MAGNETAR MODEL BY MEANS OF THE GALACTIC PULSAR POPULATION

    Energy Technology Data Exchange (ETDEWEB)

    Rea, N. [Anton Pannekoek Institute for Astronomy, University of Amsterdam, Postbus 94249, NL-1090 GE Amsterdam (Netherlands); Gullón, M.; Pons, J. A.; Miralles, J. A. [Departament de Fisica Aplicada, Universitat d’Alacant, Ap. Correus 99, E-03080 Alacant (Spain); Perna, R. [Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY 11794 (United States); Dainotti, M. G. [Physics Department, Stanford University, Via Pueblo Mall 382, Stanford, CA (United States); Torres, D. F. [Instituto de Ciencias de l’Espacio (ICE, CSIC-IEEC), Campus UAB, Carrer Can Magrans s/n, E-08193 Barcelona (Spain)

    2015-11-10

    A large fraction of Gamma-ray bursts (GRBs) displays an X-ray plateau phase within <10{sup 5} s from the prompt emission, proposed to be powered by the spin-down energy of a rapidly spinning newly born magnetar. In this work we use the properties of the Galactic neutron star population to constrain the GRB-magnetar scenario. We re-analyze the X-ray plateaus of all Swift GRBs with known redshift, between 2005 January and 2014 August. From the derived initial magnetic field distribution for the possible magnetars left behind by the GRBs, we study the evolution and properties of a simulated GRB-magnetar population using numerical simulations of magnetic field evolution, coupled with Monte Carlo simulations of Pulsar Population Synthesis in our Galaxy. We find that if the GRB X-ray plateaus are powered by the rotational energy of a newly formed magnetar, the current observational properties of the Galactic magnetar population are not compatible with being formed within the GRB scenario (regardless of the GRB type or rate at z = 0). Direct consequences would be that we should allow the existence of magnetars and “super-magnetars” having different progenitors, and that Type Ib/c SNe related to Long GRBs form systematically neutron stars with higher initial magnetic fields. We put an upper limit of ≤16 “super-magnetars” formed by a GRB in our Galaxy in the past Myr (at 99% c.l.). This limit is somewhat smaller than what is roughly expected from Long GRB rates, although the very large uncertainties do not allow us to draw strong conclusion in this respect.

  2. Colour variations in the GRB 120327A afterglow

    Science.gov (United States)

    Melandri, A.; Covino, S.; Zaninoni, E.; Campana, S.; Bolmer, J.; Cobb, B. E.; Gorosabel, J.; Kim, J.-W.; Kuin, P.; Kuroda, D.; Malesani, D.; Mundell, C. G.; Nappo, F.; Sbarufatti, B.; Smith, R. J.; Steele, I. A.; Topinka, M.; Trotter, A. S.; Virgili, F. J.; Bernardini, M. G.; D'Avanzo, P.; D'Elia, V.; Fugazza, D.; Ghirlanda, G.; Gomboc, A.; Greiner, J.; Guidorzi, C.; Haislip, J. B.; Hanayama, H.; Hanlon, L.; Im, M.; Ivarsen, K. M.; Japelj, J.; Jelínek, M.; Kawai, N.; Kobayashi, S.; Kopac, D.; LaCluyzé, A. P.; Martin-Carrillo, A.; Murphy, D.; Reichart, D. E.; Salvaterra, R.; Salafia, O. S.; Tagliaferri, G.; Vergani, S. D.

    2017-10-01

    Aims: We present a comprehensive temporal and spectral analysis of the long Swift GRB 120327A afterglow data to investigate possible causes of the observed early-time colour variations. Methods: We collected data from various instruments and telescopes in X-ray, ultraviolet, optical, and near-infrared bands, and determined the shapes of the afterglow early-time light curves. We studied the overall temporal behaviour and the spectral energy distributions from early to late times. Results: The ultraviolet, optical, and near-infrared light curves can be modelled with a single power-law component between 200 and 2 × 104 s after the burst event. The X-ray light curve shows a canonical steep-shallow-steep behaviour that is typical of long gamma-ray bursts. At early times a colour variation is observed in the ultraviolet/optical bands, while at very late times a hint of a re-brightening is visible. The observed early-time colour change can be explained as a variation in the intrinsic optical spectral index, rather than an evolution of the optical extinction. Table 2 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/607/A29

  3. AN EXTERNAL SHOCK ORIGIN OF GRB 141028A

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, J. Michael; Bégué, Damien; Ryde, Felix [The Oskar Klein Centre for Cosmoparticle Physics, AlbaNova, SE-106 91 Stockholm (Sweden); Omodei, Nicola [W. W. Hansen Experimental Physics Laboratory, Kavli Institute for Particle Astrophysics and Cosmology, Department of Physics and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States); Pe’er, Asaf [Physics Department, University College Cork, Cork (Ireland); Racusin, J. L.; Cucchiara, A., E-mail: jamesb@kth.se, E-mail: damienb@kth.se [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2016-05-10

    The prompt emission of the long, smooth, and single-pulsed gamma-ray burst, GRB 141028A, is analyzed under the guise of an external shock model. First, we fit the γ -ray spectrum with a two-component photon model, namely, synchrotron+blackbody, and then fit the recovered evolution of the synchrotron νF{sub ν} peak to an analytic model derived considering the emission of a relativistic blast wave expanding into an external medium. The prediction of the model for the νF{sub ν} peak evolution matches well with the observations. We observe the blast wave transitioning into the deceleration phase. Furthermore, we assume the expansion of the blast wave to be nearly adiabatic, motivated by the low magnetic field deduced from the observations. This allows us to recover within an order of magnitude the flux density at the νF{sub ν} peak, which is remarkable considering the simplicity of the analytic model. Under this scenario we argue that the distinction between prompt and afterglow emission is superfluous as both early-time emission and late-time emission emanate from the same source. While the external shock model is clearly not a universal solution, this analysis opens the possibility that at least some fraction of GRBs can be explained with an external shock origin of their prompt phase.

  4. Enhanced cosmological GRB rates and implications for cosmogenic neutrinos

    International Nuclear Information System (INIS)

    Yueksel, Hasan; Kistler, Matthew D.

    2007-01-01

    Gamma-ray bursts, which are among the most violent events in the Universe, are one of the few viable candidates to produce ultra high-energy cosmic rays. Recently, observations have revealed that GRBs generally originate from metal-poor, low-luminosity galaxies and do not directly trace cosmic star formation, as might have been assumed from their association with core-collapse supernovae. Several implications follow from these findings. The redshift distribution of observed GRBs is expected to peak at higher redshift (compared to cosmic star formation), which is supported by the mean redshift of the Swift GRB sample, ∼3. If GRBs are, in fact, the source of the observed UHECR, then cosmic-ray production would evolve with redshift in a stronger fashion than has been previously suggested. This necessarily leads, through the GZK process, to an enhancement in the flux of cosmogenic neutrinos, providing a near-term approach for testing the gamma-ray burst-cosmic-ray connection with ongoing and proposed UHE neutrino experiments

  5. GRB physics and cosmology with peak energy-intensity correlations

    Energy Technology Data Exchange (ETDEWEB)

    Sawant, Disha, E-mail: sawant@fe.infn.it [University of Ferrara, Via Saragat-1, Block C, Ferrara 44122 (Italy); University of Nice, 28 Avenue Valrose, Nice 06103 (France); IRAP Erasmus PhD Program, European Union and INAF - IASF Bologna, Via P. Gobetti 101, Bologna 41125 (Italy); Amati, Lorenzo, E-mail: amati@iasfbo.inaf.it [INAF - IASF Bologna, Via P. Gobetti 101, Bologna 41125 (Italy); ICRANet, Piazzale Aldo Moro-5, Rome 00185 (Italy)

    2015-12-17

    Gamma Ray Bursts (GRBs) are immensely energetic explosions radiating up to 10{sup 54} erg of energy isotropically (E{sub iso}) and they are observed within a wide range of redshift (from ∼ 0.01 up to ∼ 9). Such enormous power and high redshift point at these phenomena being highly favorable to investigate the history and evolution of our universe. The major obstacle in their application as cosmological study-tools is to find a way to standardize the GRBs, for instance similar to SNe Ia. With respect to this goal, the correlation between spectral peak energy (E{sub p,i}) and the “intensity” is a positively useful and investigated criterion. Moreover, it has been demonstrated that, through the E{sub p,i} – E{sub iso} correlation, the current data set of GRBs can already contribute to the independent evidence of the matter density Ω{sub M} being ∼ 0.3 for a flat universe scenario. We try to inspect and compare the correlations of E{sub p,i} with different intensity indicators (e.g., radiated energy, average and peak luminosity, bolometric vs. monochromatic quantities, etc.) both in terms of intrinsic dispersion and precise estimation of Ω{sub M}. The outcome of such studies are further analyzed in verifying the reliability of the correlations for both GRB physics and their standardization for cosmology.

  6. MODELING THE EARLY MULTIWAVELENGTH EMISSION IN GRB 130427A

    International Nuclear Information System (INIS)

    Fraija, N.; Lee, W.; Veres, P.

    2016-01-01

    One of the most powerful gamma-ray bursts, GRB 130427A was swiftly detected from GeV γ-rays to optical wavelengths. In the GeV band, the Large Area Telescope (LAT) on board the Fermi Gamma-Ray Space Telescope observed the highest-energy photon ever recorded of 95 GeV and a bright peak in the early phase followed by emission temporally extended for more than 20 hr. In the optical band, a bright flash with a magnitude of 7.03 ± 0.03 in the time interval from 9.31 to 19.31 s after the trigger was reported by RAPTOR in r band. We study the origin of the GeV γ-ray emission, using the multiwavelength observation detected in X-ray and optical bands. The origin of the temporally extended LAT, X-ray, and optical flux is naturally interpreted as synchrotron radiation, and the 95 GeV photon and the integral flux upper limits placed by the high-altitude water Cerenkov observatory are consistent with synchrotron self-Compton from an adiabatic forward shock propagating into the stellar wind of its progenitor. The extreme LAT peak and the bright optical flash are explained through synchrotron self-Compton and synchrotron emission from the reverse shock, respectively, when the ejecta evolves in the thick-shell regime and carries a significant magnetic field

  7. Selection effects on GRB spectral-energy correlations

    International Nuclear Information System (INIS)

    Nava, Lara; Ghirlanda, Giancarlo; Ghisellini, Gabriele

    2009-01-01

    Instrumental selection effects can act upon the estimates of the peak energy E peak obs , the fluence F and the peak flux P of GRBs. If this were the case, then the correlations involving the corresponding rest frame quantities (i.e. E peak , E obs and the peak luminosity L iso ) would be questioned. We estimated, as a function of E peak obs , the minimum peak flux necessary to trigger a GRB and the minimum fluence a burst must have to determine the value of E peak obs by considering different instruments (BATSE, Swift, BeppoSAX). We find that the latter dominates over the former. We then study the E peak obs -fluence (and flux) correlation in the observer plane. GRBs with redshift show well defined E peak obs -F and E peak obs -P correlations: in this planes the selection effects are present, but do not determine the found correlations. This is not true for Swift GRBs with redshift, for which the spectral analysis threshold does affect their distribution in the observer planes. Extending the sample to GRBs without z, we still find a significant E peak obs -F correlation, although with a larger scatter than that defined by GRBs with redshift. We find that 6% are outliers of the Amati correlation. The E peak obs -P correlation of GRBs with or without redshift is the same and no outlier is found among bursts without redshift.

  8. Computational analysis and modeling of cleavage by the immunoproteasome and the constitutive proteasome

    Directory of Open Access Journals (Sweden)

    Lafuente Esther M

    2010-09-01

    Full Text Available Abstract Background Proteasomes play a central role in the major histocompatibility class I (MHCI antigen processing pathway. They conduct the proteolytic degradation of proteins in the cytosol, generating the C-terminus of CD8 T cell epitopes and MHCI-peptide ligands (P1 residue of cleavage site. There are two types of proteasomes, the constitutive form, expressed in most cell types, and the immunoproteasome, which is constitutively expressed in mature dendritic cells. Protective CD8 T cell epitopes are likely generated by the immunoproteasome and the constitutive proteasome, and here we have modeled and analyzed the cleavage by these two proteases. Results We have modeled the immunoproteasome and proteasome cleavage sites upon two non-overlapping sets of peptides consisting of 553 CD8 T cell epitopes, naturally processed and restricted by human MHCI molecules, and 382 peptides eluted from human MHCI molecules, respectively, using N-grams. Cleavage models were generated considering different epitope and MHCI-eluted fragment lengths and the same number of C-terminal flanking residues. Models were evaluated in 5-fold cross-validation. Judging by the Mathew's Correlation Coefficient (MCC, optimal cleavage models for the proteasome (MCC = 0.43 ± 0.07 and the immunoproteasome (MCC = 0.36 ± 0.06 were obtained from 12-residue peptide fragments. Using an independent dataset consisting of 137 HIV1-specific CD8 T cell epitopes, the immunoproteasome and proteasome cleavage models achieved MCC values of 0.30 and 0.18, respectively, comparatively better than those achieved by related methods. Using ROC analyses, we have also shown that, combined with MHCI-peptide binding predictions, cleavage predictions by the immunoproteasome and proteasome models significantly increase the discovery rate of CD8 T cell epitopes restricted by different MHCI molecules, including A*0201, A*0301, A*2402, B*0702, B*2705. Conclusions We have developed models that are specific

  9. Five Years of Multi-frequency Monitoring of GRB030329 Afterglow Using the GMRT and WSRT

    International Nuclear Information System (INIS)

    Kamble, Atish; Wijers, Ralph; Rol, Evert; Horst, A. J. van der; Kouveliotou, Chryssa; Bhattacharya, D.; Chandra, C. H. Ishwara; Resmi, L.; Strom, R.

    2009-01-01

    GRB 030329 displayed one of the brightest optical afterglows ever. We have followed the radio afterglow of GRB 030329 for over 5 years using the GMRT and WSRT at low radio frequencies. This is the longest as well as the lowest frequency follow up of any GRB afterglow ever.Radio observations of a GRB afterglow provide a unique probe of the physics of the blast wave at late times, when the expansion of the fireball slows down to non-relativistic speeds. Our GMRT-WSRT observations suggest that the afterglow of GRB030329 entered the non-relativistic phase around 60 days after the burst. The estimate of the fireball energy content, ∼10 51 erg, in this near-isotropic phase is much less susceptible to the collimation-related uncertainties arising in the relativistic phase. We have also been closely monitoring the evolution of the afterglow to look for possible signatures of emission from a counter jet, but no conclusive evidence has so far been found.

  10. ON THE HOST GALAXY OF GRB 150101B AND THE ASSOCIATED ACTIVE GALACTIC NUCLEUS

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Chen [Department of Physics, Xiamen University, Xiamen (China); Fang, Taotao; Wang, Junfeng; Liu, Tong; Jiang, Xiaochuan, E-mail: fangt@xmu.edu.cn [Department of Astronomy and Institute of Theoretical Physics and Astrophysics, Xiamen University, Xiamen (China)

    2016-06-20

    We present a multi-wavelength analysis of the host galaxy of short-duration gamma-ray burst (GRB) 150101B. Follow-up optical and X-ray observations suggested that the host galaxy, 2MASX J12320498-1056010, likely harbors low-luminosity active galactic nuclei (AGNs). Our modeling of the spectral energy distribution has confirmed the nature of the AGN, making it the first reported GRB host that contains an AGN. We have also found the host galaxy is a massive elliptical galaxy with stellar population of ∼5.7 Gyr, one of the oldest among the short-duration GRB hosts. Our analysis suggests that the host galaxy can be classified as an X-ray bright, optically normal galaxy, and the central AGN is likely dominated by a radiatively inefficient accretion flow. Our work explores an interesting connection that may exist between GRB and AGN activities of the host galaxy, which can help in understanding the host environment of the GRB events and the roles of AGN feedback.

  11. GRB 170817A as a jet counterpart to gravitational wave trigger GW 170817

    Science.gov (United States)

    Lamb, Gavin P.; Kobayashi, Shiho

    2018-05-01

    Fermi/GBM (Gamma-ray Burst Monitor) and INTEGRAL (the International Gamma-ray Astrophysics Laboratory) reported the detection of the γ-ray counterpart, GRB 170817A, to the LIGO (Light Interferometer Gravitational-wave Observatory)/Virgo gravitational wave detected binary neutron star merger, GW 170817. GRB 170817A is likely to have an internal jet or another origin such as cocoon emission, shock-breakout, or a flare from a viscous disc. In this paper we assume that the γ-ray emission is caused by energy dissipation within a relativistic jet and we model the afterglow synchrotron emission from a reverse- and forward-shock in the outflow. We show the afterglow for a low-luminosity γ-ray burst (GRB) jet with a high Lorentz-factor (Γ); a low-Γ and low-kinetic energy jet; a low-Γ, high kinetic energy jet; structured jets viewed at an inclination within the jet-half-opening angle; and an off-axis `typical' GRB jet. All jet models will produce observable afterglows on various timescales. The late-time afterglow from 10-110 days can be fit by a Gaussian structured jet viewed at a moderate inclination, however the GRB is not directly reproduced by this model. These jet afterglow models can be used for future GW detected NS merger counterparts with a jet afterglow origin.

  12. Revealing Physical Activity of GRB Central Engine with Macronova/Kilonova Data

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Zhao-Qiang; Jin, Zhi-Ping; Liang, Yun-Feng; Li, Xiang; Fan, Yi-Zhong; Wei, Da-Ming, E-mail: yzfan@pmo.ac.cn, E-mail: dmwei@pmo.ac.cn [Key Laboratory of dark Matter and Space Astronomy, Purple Mountain Observatory, Chinese Academy of Science, Nanjing 210008 (China)

    2017-02-01

    The modeling of Li-Paczyński macronova/kilonova signals gives a reasonable estimate on the neutron-rich material ejected during the neutron star mergers. Usually the accretion disk is more massive than the macronova ejecta, with which the efficiencies of converting the disk mass into prompt emission of three merger-driven GRBs can hence be directly constrained. Supposing the macronovae/kilonovae associated with GRB 050709, GRB 060614, and GRB 130603B arose from radioactive decay of the r -process material, the upper limit on energy conversion efficiencies are found to be as low as ∼10{sup −6}–10{sup −4}. Moreover, for all three events, neutrino annihilation is likely powerful enough to account for the brief gamma-ray flashes. Neutrino annihilation can also explain the “extended” emission lasting ∼100 s in GRB 050709, but does not work for the one in GRB 060614. These progresses demonstrate that the macronova can serve as a novel probe of the central engine activity.

  13. Using GRB 080723B to cross-calibrate Fermi/GBM and INTEGRAL

    International Nuclear Information System (INIS)

    Kienlin, A. von; Briggs, M. S.; Connoughton, V.; Preece, R. D.; McBreen, S.; Sazonov, Sergey; Tsygankov, Sergey; Wilson-Hodge, C. A.

    2009-01-01

    On July 23, 2008 GRB 080723B, a bright GRB lasting about 105 s was detected by the INTEGRAL burst alert system. This burst was also detected by the Fermi Gamma-ray burst monitor. At this time no Fermi/GBM GCN notices were distributed to the public because Fermi was still in commissioning phase. The simultaneous detection of a bright GRB by both satellites gives us the opportunity to cross-calibrate the GBM with the already well-calibrated instruments on-board INTEGRAL, the Spectrometer SPI and the Imager IBIS. Time-resolved spectroscopy of this long and structured GRB is of special importance because Fermi was slewing during the GRB was still ongoing. In this paper we present a first and still preliminary analysis of the GBM spectra and compare them to those obtained by SPI for the same selection of time intervals. A more accurate cross-calibration will be forthcoming when the improved in-flight calibration of GBM is available and the corresponding data and responses can be reprocessed.

  14. ON THE HOST GALAXY OF GRB 150101B AND THE ASSOCIATED ACTIVE GALACTIC NUCLEUS

    International Nuclear Information System (INIS)

    Xie, Chen; Fang, Taotao; Wang, Junfeng; Liu, Tong; Jiang, Xiaochuan

    2016-01-01

    We present a multi-wavelength analysis of the host galaxy of short-duration gamma-ray burst (GRB) 150101B. Follow-up optical and X-ray observations suggested that the host galaxy, 2MASX J12320498-1056010, likely harbors low-luminosity active galactic nuclei (AGNs). Our modeling of the spectral energy distribution has confirmed the nature of the AGN, making it the first reported GRB host that contains an AGN. We have also found the host galaxy is a massive elliptical galaxy with stellar population of ∼5.7 Gyr, one of the oldest among the short-duration GRB hosts. Our analysis suggests that the host galaxy can be classified as an X-ray bright, optically normal galaxy, and the central AGN is likely dominated by a radiatively inefficient accretion flow. Our work explores an interesting connection that may exist between GRB and AGN activities of the host galaxy, which can help in understanding the host environment of the GRB events and the roles of AGN feedback.

  15. Can laccases catalyze bond cleavage in lignin?

    DEFF Research Database (Denmark)

    Munk, Line; Sitarz, Anna Katarzyna; Kalyani, Dayanand

    2015-01-01

    illustrations of the putative laccase catalyzed reactions, including the possible reactions of the reactive radical intermediates taking place after the initial oxidation of the phenol-hydroxyl groups, we show that i) Laccase activity is able to catalyze bond cleavage in low molecular weight phenolic lignin......-substituted phenols, benzenethiols, polyphenols, and polyamines, which may be oxidized. In addition, the currently available analytical methods that can be used to detect enzyme catalyzed changes in lignin are summarized, and an improved nomenclature for unequivocal interpretation of the action of laccases on lignin...

  16. Abyssal fiction: common shares, colonial cleavages

    Directory of Open Access Journals (Sweden)

    Alexandre Montaury

    2016-12-01

    Full Text Available The paper aims to develop a reflection on the interaction between the legacies of colonialism and traditional symbolic and cultural practices in African Portuguese-speaking spaces. From a preliminary analysis of fictional texts of wide circulation in Brazil, aims to examine the cleavages, or “abyssal lines” that constitute experiences printed in the daily life of the former Portuguese colony of Cape Verde, Mozambique and Angola.---DOI: http://dx.doi.org/10.21881/abriluff.2016n17a378

  17. Transcriptional down-regulation and rRNA cleavage in Dictyostelium discoideum mitochondria during Legionella pneumophila infection.

    Directory of Open Access Journals (Sweden)

    Chenyu Zhang

    2009-05-01

    Full Text Available Bacterial pathogens employ a variety of survival strategies when they invade eukaryotic cells. The amoeba Dictyostelium discoideum is used as a model host to study the pathogenic mechanisms that Legionella pneumophila, the causative agent of Legionnaire's disease, uses to kill eukaryotic cells. Here we show that the infection of D. discoideum by L. pneumophila results in a decrease in mitochondrial messenger RNAs, beginning more than 8 hours prior to detectable host cell death. These changes can be mimicked by hydrogen peroxide treatment, but not by other cytotoxic agents. The mitochondrial large subunit ribosomal RNA (LSU rRNA is also cleaved at three specific sites during the course of infection. Two LSU rRNA fragments appear first, followed by smaller fragments produced by additional cleavage events. The initial LSU rRNA cleavage site is predicted to be on the surface of the large subunit of the mitochondrial ribosome, while two secondary sites map to the predicted interface with the small subunit. No LSU rRNA cleavage was observed after exposure of D. discoideum to hydrogen peroxide, or other cytotoxic chemicals that kill cells in a variety of ways. Functional L. pneumophila type II and type IV secretion systems are required for the cleavage, establishing a correlation between the pathogenesis of L. pneumophila and D. discoideum LSU rRNA destruction. LSU rRNA cleavage was not observed in L. pneumophila infections of Acanthamoeba castellanii or human U937 cells, suggesting that L. pneumophila uses distinct mechanisms to interrupt metabolism in different hosts. Thus, L. pneumophila infection of D. discoideum results in dramatic decrease of mitochondrial RNAs, and in the specific cleavage of mitochondrial rRNA. The predicted location of the cleavage sites on the mitochondrial ribosome suggests that rRNA destruction is initiated by a specific sequence of events. These findings suggest that L. pneumophila specifically disrupts mitochondrial

  18. NuSTARobservations of grb 130427a establish a single component synchrotron afterglow origin for the late optical to multi-gev emission

    DEFF Research Database (Denmark)

    Kouveliotou, C.; Granot, J.; Racusin, J. L.

    2013-01-01

    GRB 130427A occurred in a relatively nearby galaxy; its prompt emission had the largest GRB fluence ever recorded. The afterglow of GRB 130427A was bright enough for the Nuclear Spectroscopic Telescope ARray (NuSTAR) to observe it in the 3-79 keV energy range long after its prompt emission (simil...

  19. The very red afterglow of GRB 000418: Further evidence for dust extinction in a gamma-ray burst host galaxy

    DEFF Research Database (Denmark)

    Klose, S.; Stecklum, B.; Masetti, N.

    2000-01-01

    We report near-infrared and optical follow-up observations of the afterglow of the GRB 000418 starting 2.5 days after the occurrence of the burst and extending over nearly 7 weeks. GRB 000418 represents the second case for which the afterglow was initially identified by observations in the near......) bursts are associated with events in star-forming regions....

  20. Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

    DEFF Research Database (Denmark)

    Abbott, B. P.; Abbott, R.; Abbott, T. D.

    2017-01-01

    On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gam...

  1. Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

    NARCIS (Netherlands)

    Abbott, B. P.; Abbott, R.; Abbott, T. D.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Afrough, M.; Agarwal, B.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Allen, B.; Allen, G.; Allocca, A.; Aloy, M. A.; Altin, P. A.; Amato, A.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Angelova, S. V.; Antier, S.; Appert, S.; Arai, K.; Araya, M. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Ascenzi, S.; Ashton, G.; Ast, M.; Aston, S. M.; Astone, P.; Atallah, D. V.; Aufmuth, P.; Aulbert, C.; AultONeal, K.; Austin, C.; Avila-Alvarez, A.; Babak, S.; Bacon, P.; Bader, M. K. M.; Bae, S.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Banagiri, S.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, D.; Barkett, K.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Bawaj, M.; Bayley, J. C.; Bazzan, M.; Becsy, B.; Beer, C.; Bejger, M.; Belahcene, I.; Bell, A. S.; Berger, B. K.; Bergmann, G.; Bero, J. J.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Billman, C. R.; Birch, J.; Birney, R.; Birnholtz, O.; Biscans, S.; Biscoveanu, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blackman, J.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bloemen, S.; Bock, O.; Bode, N.; Boer, M.; Bogaert, G.; Bohe, A.; Bondu, F.; Bonilla, E.; Bonnand, R.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, S.; Bossie, K.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Broida, J. E.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brunett, S.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cabero, M.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Bustillo, J. Calderon; Callister, T. A.; Calloni, E.; Camp, J. B.; Canepa, M.; Canizares, P.; Cannon, K. C.; Cao, H.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Carney, M. F.; Diaz, J. Casanueva; Casentini, C.; Caudill, S.; Cavaglia, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C. B.; Cerda-Duran, P.; Cerretani, G.; Cesarini, E.; Chamberlin, S. J.; Chan, M.; Chao, S.; Charlton, P.; Chase, E.; Chassande-Mottin, E.; Chatterjee, D.; Chatziioannou, K.; Cheeseboro, B. D.; Chen, H. Y.; Chen, X.; Chen, Y.; Cheng, H. -P.; Chia, H.; Chincarini, A.; Chiummo, A.; Chmiel, T.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chua, A. J. K.; Chua, S.; Chung, A. K. W.; Chung, S.; Ciani, G.; Ciolfi, R.; Cirelli, C. E.; Cirone, A.; Clara, F.; Clark, J. A.; Clearwater, P.; Cleva, F.; Cocchieri, C.; Coccia, E.; Cohadon, P. -F.; Cohen, D.; Colla, A.; Collette, C. G.; Cominsky, L. R.; Constancio, M., Jr.; Conti, L.; Cooper, S. J.; Corban, P.; Corbitt, T. R.; Cordero-Carrion, I.; Corley, K. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, C. A.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J. -P.; Countryman, S. T.; Couvares, P.; Covas, P. B.; Cowan, E. E.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Creighton, J. D. E.; Creighton, T. D.; Cripe, J.; Crowder, S. G.; Cullen, T. J.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dal Canton, T.; Dalya, G.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Dasgupta, A.; Costa, C. F. Da Silva; Dattilo, V.; Dave, I.; Davier, M.; Davis, D.; Daw, E. J.; Day, B.; De, S.; Debra, D.; Degallaix, J.; De laurentis, M.; Deleglise, S.; Del Pozzo, W.; Demos, N.; Denker, T.; Dent, T.; De Pietri, R.; Dergachev, V.; De Rosa, R.; DeRosa, R. T.; De Rossi, C.; DeSalvo, R.; de Varona, O.; Devenson, J.; Dhurandhar, S.; Diaz, M. C.; Di Fiore, L.; Di Giovanni, M.; Di Girolamo, T.; Di Lieto, A.; Di Pace, S.; Di Palma, I.; Di Renzo, F.; Doctor, Z.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Douglas, R.; Alvarez, M. Dovale; Downes, T. P.; Drago, M.; Dreissigacker, C.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dupej, P.; Dwyer, S. E.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H. -B.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Eisenstein, R. A.; Essick, R. C.; Estevez, D.; Etienne, Z. B.; Etzel, T.; Evans, M.; Evans, T. M.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.; Farinon, S.; Farr, B.; Farr, W. M.; Fauchon-Jones, E. J.; Favata, M.; Fays, M.; Fee, C.; Fehrmann, H.; Feicht, J.; Fejer, M. M.; Fernandez-Galiana, A.; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Finstad, D.; Fiori, I.; Fiorucci, D.; Fishbach, M.; Fisher, R. P.; Fitz-Axen, M.; Flaminio, R.; Fletcher, M.; Fong, H.; Font, J. A.; Forsyth, P. W. F.; Forsyth, S. S.; Fournier, J. -D.; Frasca, S.; Frasconi, F.; Frei, Z.; Freise, A.; Frey, R.; Frey, V.; Fries, E. M.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Gabbard, H.; Gadre, B. U.; Gaebel, S. M.; Gair, J. R.; Gammaitoni, L.; Ganija, M. R.; Gaonkar, S. G.; Garcia-Quiros, C.; Garufi, F.; Gateley, B.; Gaudio, S.; Gaur, G.; Gayathri, V.; Gehrels, N.; Gemme, G.; Genin, E.; Gennai, A.; George, D.; George, J.; Gergely, L.; Germain, V.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.; Glover, L.; Goetz, E.; Goetz, R.; Gomes, S.; Goncharov, B.; Gonzalez, G.; Castro, J. M. Gonzalez; Gopakumar, A.; Gorodetsky, M. L.; Gossan, S. E.; Gosselin, M.; Gouaty, R.; Grado, A.; Graef, C.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greco, G.; Green, A. C.; Gretarsson, E. M.; Groot, P.; Grote, H.; Grunewald, S.; Gruning, P.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Halim, O.; Hall, B. R.; Hall, E. D.; Hamilton, E. Z.; Hammond, G.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hannuksela, O. A.; Hanson, J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.; Haster, C. -J.; Haughian, K.; Healy, J.; Heidmann, A.; Heintze, M. C.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennig, J.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hinderer, T.; Hoak, D.; Hofman, D.; Holt, K.; Holz, D. E.; Hopkins, P.; Horst, C.; Hough, J.; Houston, E. A.; Howell, E. J.; Hreibi, A.; Hu, Y. M.; Huerta, E. A.; Huet, D.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh-Dinh, T.; Indik, N.; Inta, R.; Intini, G.; Isa, H. N.; Isac, J. -M.; Isi, M.; Iyer, B. R.; Izumi, K.; Jacqmin, T.; Jani, K.; Jaranowski, P.; Jawahar, S.; Jimenez-Forteza, F.; Johnson, W. W.; Johnson-McDaniel, N. K.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Kalaghatgi, C. V.; Kalogera, V.; Kamai, B.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kapadia, S. J.; Karki, S.; Karvinen, K. S.; Kasprzack, M.; Kastaun, W.; Katolik, M.; Katsavounidis, E.; Katzman, W.; Kaufer, S.; Kawabe, K.; Kefelian, F.; Keitel, D.; Kemball, A. J.; Kennedy, R.; Kent, C.; Key, J. S.; Khalili, F. Y.; Khan, I.; Khan, S.; Khan, Z.; Khazanov, E. A.; Kijbunchoo, N.; Kim, Chunglee; Kim, J. C.; Kim, K.; Kim, W.; Kim, W. S.; Kim, Y. -M.; Kimbrell, S. J.; King, E. J.; King, P. J.; Kinley-Hanlon, M.; Kirchhoff, R.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Knowles, T. D.; Koch, P.; Koehlenbeck, S. M.; Koley, S.; Kondrashov, V.; Kontos, A.; Korobko, M.; Korth, W. Z.; Kowalska, I.; Kozak, D. B.; Kraemer, C.; Kringel, V.; Krishnan, B.; Krolak, A.; Kuehn, G.; Kumar, P.; Kumar, R.; Kumar, S.; Kuo, L.; Kutynia, A.; Kwang, S.; Lackey, B. D.; Lai, K. H.; Landry, M.; Lang, R. N.; Lange, J.; Lantz, B.; Lanza, R. K.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lee, C. H.; Lee, H. K.; Lee, H. M.; Lee, H. W.; Lee, K.; Lehmann, J.; Lenon, A.; Leonardi, M.; Leroy, N.; Letendre, N.; Levin, Y.; Li, T. G. F.; Linker, S. D.; Littenberg, T. B.; Liu, J.; Lo, R. K. L.; Lockerbie, N. A.; London, L. T.; Lord, J. E.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lueck, H.; Lumaca, D.; Lundgren, A. P.; Lynch, R.; Ma, Y.; Macas, R.; Macfoy, S.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Hernandez, I. Magana; Magana-Sandoval, F.; Zertuche, L. Magana; Magee, R. M.; Majorana, E.; Maksimovic, I.; Man, N.; Mandic, V.; Mangano, V.; Mansell, G. L.; Manske, M.; Mantovani, M.; Marchesoni, F.; Marion, F.; Marka, S.; Marka, Z.; Markakis, C.; Markosyan, A. S.; Markowitz, A.; Maros, E.; Marquina, A.; Martelli, F.; Martellini, L.; Martin, I. W.; Martin, R. M.; Martynov, D. V.; Mason, K.; Massera, E.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matas, A.; Matichard, F.; Matone, L.; Mavalvala, N.; Mazumder, N.; McCarthy, R.; McClelland, D. E.; McCormick, S.; McCuller, L.; McGuire, S. C.; McIntyre, G.; McIver, J.; McManus, D. J.; McNeill, L.; Mcrae, T.; McWilliams, S. T.; Meacher, D.; Meadors, G. D.; Mehmet, M.; Meidam, J.; Mejuto-Villa, E.; Melatos, A.; Mendell, G.; Mercer, R. A.; Merilh, E. L.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Metzdorff, R.; Meyers, P. M.; Miao, H.; Michel, C.; Middleton, H.; Mikhailov, E. E.; Milano, L.; Miller, A. L.; Miller, B. B.; Miller, J.; Millhouse, M.; Milovich-Goff, M. C.; Minazzoli, O.; Minenkov, Y.; Ming, J.; Mishra, C.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moffa, D.; Moggi, A.; Mogushi, K.; Mohan, M.; Mohapatra, S. R. P.; Montani, M.; Moore, C. J.; Moraru, D.; Moreno, G.; Morriss, S. R.; Mours, B.; Mow-Lowry, C. M.; Mueller, G.; Muir, A. W.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, S.; Mukund, N.; Mullavey, A.; Munch, J.; Muniz, E. A.; Muratore, M.; Murray, P. G.; Napier, K.; Nardecchia, I.; Naticchioni, L.; Nayak, R. K.; Neilson, J.; Nelemans, G.; Nelson, T. J. N.; Nery, M.; Neunzert, A.; Nevin, L.; Newport, J. M.; Newton, G.; Ng, K. K. Y.; Nguyen, T. T.; Nichols, D.; Nielsen, A. B.; Nissanke, S.; Nitz, A.; Noack, A.; Nocera, F.; Nolting, D.; North, C.; Nuttall, L. K.; Oberling, J.; O'Dea, G. D.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Okada, M. A.; Oliver, M.; Oppermann, P.; Oram, Richard J.; O'Reilly, B.; Ormiston, R.; Ortega, L. F.; O'Shaughnessy, R.; Ossokine, S.; Ottaway, D. J.; Overmier, H.; Owen, B. J.; Pace, A. E.; Page, J.; Page, M. A.; Pai, A.; Pai, S. A.; Palamos, J. R.; Palashov, O.; Palomba, C.; Pal-Singh, A.; Pan, Howard; Pan, Huang-Wei; Pang, B.; Pang, P. T. H.; Pankow, C.; Pannarale, F.; Pant, B. C.; Paoletti, F.; Paoli, A.; Papa, M. A.; Parida, A.; Parker, W.; Pascucci, D.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Patil, M.; Patricelli, B.; Pearlstone, B. L.; Pedraza, M.; Pedurand, R.; Pekowsky, L.; Pele, A.; Penn, S.; Perez, C. J.; Perreca, A.; Perri, L. M.; Pfeiffer, H. P.; Phelps, M.; Piccinni, O. J.; Pichot, M.; Piergiovanni, F.; Pierro, V.; Pillant, G.; Pinard, L.; Pinto, I. M.; Pirello, M.; Pitkin, M.; Poe, M.; Poggiani, R.; Popolizio, P.; Porter, E. K.; Post, A.; Powell, J.; Prasad, J.; Pratt, J. W. W.; Pratten, G.; Predoi, V.; Prestegard, T.; Prijatelj, M.; Principe, M.; Privitera, S.; Prodi, G. A.; Prokhorov, L. G.; Puncken, O.; Punturo, M.; Puppo, P.; Puerrer, M.; Qi, H.; Quetschke, V.; Quintero, E. A.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Radkins, H.; Raffai, P.; Raja, S.; Rajan, C.; Rajbhandari, B.; Rakhmanov, M.; Ramirez, K. E.; Ramos-Buades, A.; Rapagnani, P.; Raymond, V.; Razzano, M.; Read, J.; Regimbau, T.; Rei, L.; Reid, S.; Reitze, D. H.; Ren, W.; Reyes, S. D.; Ricci, F.; Ricker, P. M.; Rieger, S.; Riles, K.; Rizzo, M.; Robertson, N. A.; Robie, R.; Robinet, F.; Rocchi, A.; Rolland, L.; Rollins, J. G.; Roma, V. J.; Romano, R.; Romel, C. L.; Romie, J. H.; Rosinska, D.; Ross, M. P.; Rowan, S.; Ruediger, A.; Ruggi, P.; Rutins, G.; Ryan, K.; Sachdev, S.; Sadecki, T.; Sadeghian, L.; Sakellariadou, M.; Salconi, L.; Saleem, M.; Salemi, F.; Samajdar, A.; Sammut, L.; Sampson, L. M.; Sanchez, E. J.; Sanchez, L. E.; Sanchis-Gual, N.; Sandberg, V.; Sanders, J. R.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Sauter, O.; Savage, R. L.; Sawadsky, A.; Schale, P.; Scheel, M.; Scheuer, J.; Schmidt, J.; Schmidt, P.; Schnabel, R.; Schofield, R. M. S.; Schoenbeck, A.; Schreiber, E.; Schuette, D.; Schulte, B. W.; Schutz, B. F.; Schwalbe, S. G.; Scott, J.; Scott, S. M.; Seidel, E.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sequino, V.; Sergeev, A.; Shaddock, D. A.; Shaffer, T. J.; Shah, A. A.; Shahriar, M. S.; Shaner, M. B.; Shao, L.; Shapiro, B.; Shawhan, P.; Sheperd, A.; Shoemaker, D. H.; Shoemaker, D. M.; Siellez, K.; Siemens, X.; Sieniawska, M.; Sigg, D.; Silva, A. D.; Singer, L. P.; Singh, A.; Singhal, A.; Sintes, A. M.; Slagmolen, B. J. J.; Smith, B.; Smith, R. J. E.; Smith, R. J. E.; Somala, S.; Son, E. J.; Sonnenberg, J. A.; Sorazu, B.; Sorrentino, F.; Souradeep, T.; Spencer, A. P.; Srivastava, A. K.; Staats, K.; Staley, A.; Steinke, M.; Steinlechner, J.; Steinlechner, S.; Steinmeyer, D.; Stevenson, S. P.; Stone, R.; Stops, D. J.; Strain, K. A.; Stratta, G.; Strigin, S. E.; Strunk, A.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Sun, L.; Sunil, S.; Suresh, J.; Sutton, P. J.; Swinkels, B. L.; Szczepanczyk, M. J.; Tacca, M.; Tait, S. C.; Talbot, C.; Talukder, D.; Tanner, D. B.; Tapai, M.; Taracchini, A.; Tasson, J. D.; Taylor, J. A.; Taylor, R.; Tewari, S. V.; Theeg, T.; Thies, F.; Thomas, E. G.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, S.; Tiwari, V.; Tokmakov, K. V.; Toland, K.; Tonelli, M.; Tornasi, Z.; Torres-Forne, A.; Torrie, C. I.; Toyra, D.; Travasso, F.; Traylor, G.; Trinastic, J.; Tringali, M. C.; Trozzo, L.; Tsang, K. W.; Tse, M.; Tso, R.; Tsukada, L.; Tsuna, D.; Tuyenbayev, D.; Ueno, K.; Ugolini, D.; Unnikrishnan, C. S.; Urban, A. L.; Usman, S. A.; Vahlbruch, H.; Vajente, G.; Valdes, G.; van Bakel, N.; van Beuzekom, M.; Van den Brand, J. F. J.; Van den Broeck, C.; Vander-Hyde, D. C.; Van der Schaaf, L.; van Heijningen, J. V.; van Veggel, A. A.; Vardaro, M.; Varma, V.; Vass, S.; Vasuth, M.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Venugopalan, G.; Verkindt, D.; Vetrano, F.; Vicere, A.; Viets, A. D.; Vinciguerra, S.; Vine, D. J.; Vinet, J. -Y.; Vitale, S.; Vo, T.; Vocca, H.; Vorvick, C.; Vyatchanin, S. P.; Wade, A. R.; Wade, L. E.; Wade, M.; Walet, R.; Walker, M.; Wallace, L.; Walsh, S.; Wang, G.; Wang, H.; Wang, J. Z.; Wang, W. H.; Wang, Y. F.; Ward, R. L.; Warner, J.; Was, M.; Watchi, J.; Weaver, B.; Wei, L. -W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Wen, L.; Wessel, E. K.; Wessels, P.; Westerweck, J.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; Whiting, B. F.; Whittle, C.; Wilken, D.; Williams, D.; Williams, R. D.; Williamson, A. R.; Willis, J. L.; Willke, B.; Wimmer, M. H.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Woehler, J.; Wofford, J.; Wong, K. W. K.; Worden, J.; Wright, J. L.; Wu, D. S.; Wysocki, D. M.; Xiao, S.; Yamamoto, H.; Yancey, C. C.; Yang, L.; Yap, M. J.; Yazback, M.; Yu, Hang; Yu, Haocun; Yvert, M.; Zadrozny, A.; Zanolin, M.; Zelenova, T.; Zendri, J. -P.; Zevin, M.; Zhang, L.; Zhang, M.; Zhang, T.; Zhang, Y. -H.; Zhao, C.; Zhou, M.; Zhou, Z.; Zhu, S. J.; Zhu, X. J.; Zimmerman, A. B.; Zucker, M. E.; Zweizig, J.; Burns, E.; Veres, P.; Kocevski, D.; Racusin, J.; Goldstein, A.; Connaughton, V.; Briggs, M. S.; Blackburn, L.; Hamburg, R.; Hui, C. M.; von Kienlin, A.; McEnery, J.; Preece, R. D.; Wilson-Hodge, C. A.; Bissaldi, E.; Cleveland, W. H.; Gibby, M. H.; Giles, M. M.; Kippen, R. M.; McBreen, S.; Meegan, C. A.; Paciesas, W. S.; Poolakkil, S.; Roberts, O. J.; Stanbro, M.; Savchenko, V.; Ferrigno, C.; Kuulkers, E.; Bazzano, A.; Bozzo, E.; Brandt, S.; Chenevez, J.; Courvoisier, T. J. -L.; Diehl, R.; Domingo, A.; Hanlon, L.; Jourdain, E.; Laurent, P.; Lebrun, F.; Lutovinov, A.; Mereghetti, S.; Natalucci, L.; Rodi, J.; Roques, J. -P.; Sunyaev, R.; Ubertini, P.

    2017-01-01

    On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International

  2. The optical afterglow of the short gamma-ray burst GRB 050709.

    Science.gov (United States)

    Hjorth, Jens; Watson, Darach; Fynbo, Johan P U; Price, Paul A; Jensen, Brian L; Jørgensen, Uffe G; Kubas, Daniel; Gorosabel, Javier; Jakobsson, Páll; Sollerman, Jesper; Pedersen, Kristian; Kouveliotou, Chryssa

    2005-10-06

    It has long been known that there are two classes of gamma-ray bursts (GRBs), mainly distinguished by their durations. The breakthrough in our understanding of long-duration GRBs (those lasting more than approximately 2 s), which ultimately linked them with energetic type Ic supernovae, came from the discovery of their long-lived X-ray and optical 'afterglows', when precise and rapid localizations of the sources could finally be obtained. X-ray localizations have recently become available for short (duration burst: GRB 050709. The optical afterglow was localized with subarcsecond accuracy, and lies in the outskirts of a blue dwarf galaxy. The optical and X-ray afterglow properties 34 h after the GRB are reminiscent of the afterglows of long GRBs, which are attributable to synchrotron emission from ultrarelativistic ejecta. We did not, however, detect a supernova, as found in most nearby long GRB afterglows, which suggests a different origin for the short GRBs.

  3. Regioselectivity in the Reductive Bond Cleavage of Diarylalkylsulfonium Salts

    DEFF Research Database (Denmark)

    Kampmeier, Jack; Mansurul Hoque, AKM; D. Saeva, Franklin

    2009-01-01

    products vary from regiospecific alkyl cleavage to predominant aryl cleavage as a function of the potential of the reducing agent. We conclude that differences between the reductive cleavages of mono- and diarylsulfonium salts are direct consequences of the structures of the sulfuranyl radical......- tolylethylsulfonium and di-4-tolyl-2-phenylethylsulfonium salts by a variety of one-electron reducing agents ranging in potential from -0.77 to +2.5 eV (vs SCE) and including thermal reductants, indirect electrolyses mediated by a series of cyanoaromatics, and excited singlet states. We report that the cleavage...... intermediates and the bond dissociation energies of the alkyl and aryl bonds. Competitions between the rates of cleavage and oxidation of the intermediate sulfuranyl radicals and between concerted and stepwise mechanisms are discussed to explain the variations in bond cleavage products as a function...

  4. DUST PROPERTIES IN THE AFTERGLOW OF GRB 071025 AT z {approx} 5

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Minsung; Im, Myungshin [Center for the Exploration of the Origin of the Universe (CEOU), Astronomy Program, Department of Physics and Astronomy, Seoul National University, Shillim-Dong, Kwanak-Gu, Seoul 151-742 (Korea, Republic of); Lee, Induk; Urata, Yuji [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Huang, Kuiyun; Hirashita, Hiroyuki [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 10617, Taiwan (China); Fan Xiaohui; Jiang Linhua, E-mail: msjang.astro@gmail.com, E-mail: mim@astro.snu.ac.kr [Steward Observatory, University of Arizona, Tucson, AZ (United States)

    2011-11-15

    At high redshift, the universe is so young that core-collapse supernovae (SNe) are suspected to be the dominant source of dust production. However, some observations indicate that the dust production by SNe is an inefficient process, casting doubts on the existence of abundant SNe-dust in the early universe. Recently, Perley et al. reported that the afterglow of GRB 071025-an unusually red gamma-ray burst (GRB) at z {approx} 5-shows evidence for SNe-produced dust. Since this is perhaps the only high-redshift GRB exhibiting compelling evidence for SNe-dust but the result could easily be affected by small systematics in photometry, we re-examined the extinction properties of GRB 071025 using our own optical/near-infrared data at a different epoch. In addition, we tested SNe-dust models with different progenitor masses and dust destruction efficiencies to constrain the dust formation mechanisms. By searching for the best-fit model of the afterglow spectral energy distribution, we confirm the previous claim that the dust in GRB 071025 is most likely to originate from SNe. We also find that the SNe-dust model of 13 or 25 M{sub Sun} without dust destruction fits the extinction property of GRB 071025 best, while pair-instability SNe models with a 170 M{sub Sun} progenitor poorly fit the data. Our results indicate that, at least in some systems at high redshift, SNe with intermediate initial masses within 10-30 M{sub Sun} were the main contributors for the dust enrichment, and the dust destruction effect due to reverse shock was negligible.

  5. The Supercritical Pile Gamma-Ray Burst Model: The GRB Afterglow Steep Decline and Plateau Phase

    Science.gov (United States)

    Sultana, Joseph; Kazanas, D.; Mastichiadis, A.

    2013-01-01

    We present a process that accounts for the steep decline and plateau phase of the Swift X-Ray Telescope (XRT) light curves, vexing features of gamma-ray burst (GRB) phenomenology. This process is an integral part of the "supercritical pile" GRB model, proposed a few years ago to account for the conversion of the GRB kinetic energy into radiation with a spectral peak at E(sub pk) is approx. m(sub e)C(exp 2). We compute the evolution of the relativistic blast wave (RBW) Lorentz factor Gamma to show that the radiation-reaction force due to the GRB emission can produce an abrupt, small (approx. 25%) decrease in Gamma at a radius that is smaller (depending on conditions) than the deceleration radius R(sub D). Because of this reduction, the kinematic criticality criterion of the "supercritical pile" is no longer fulfilled. Transfer of the proton energy into electrons ceases and the GRB enters abruptly the afterglow phase at a luminosity smaller by approx. m(sub p)/m(sub e) than that of the prompt emission. If the radius at which this slow-down occurs is significantly smaller than R(sub D), the RBW internal energy continues to drive the RBW expansion at a constant (new) Gamma and its X-ray luminosity remains constant until R(sub D) is reached, at which point it resumes its more conventional decay, thereby completing the "unexpected" XRT light curve phase. If this transition occurs at R is approx. equal to R(sub D), the steep decline is followed by a flux decrease instead of a "plateau," consistent with the conventional afterglow declines. Besides providing an account of these peculiarities, the model suggests that the afterglow phase may in fact begin before the RBW reaches R is approx. equal to R(sub D), thus providing novel insights into GRB phenomenology.

  6. GRB 080503 LATE AFTERGLOW RE-BRIGHTENING: SIGNATURE OF A MAGNETAR-POWERED MERGER-NOVA

    International Nuclear Information System (INIS)

    Gao, He; Ding, Xuan; Wu, Xue-Feng; Dai, Zi-Gao; Zhang, Bing

    2015-01-01

    GRB 080503 is a short gamma-ray burst (GRB) detected by Swift and has been classified as a GRB originating from a compact star merger. The soft extended emission and the simultaneous late re-brightening in both the X-ray and optical afterglow light curves raise interesting questions regarding its physical origin. We show that the broadband data of GRB 080503 can be well explained within the framework of the double neutron star merger model, provided that the merger remnant is a rapidly rotating massive neutron star with an extremely high magnetic field (i.e., a millisecond magnetar). We show that the late optical re-brightening is consistent with the emission from a magnetar-powered “merger-nova.” This adds one more case to the growing sample of merger-novae associated with short GRBs. The soft extended emission and the late X-ray excess emission are well connected through a magnetar dipole spin-down luminosity evolution function, suggesting that direct magnetic dissipation is the mechanism to produce these X-rays. The X-ray emission initially leaks from a hole in the merger ejecta pierced by the short GRB jet. The hole subsequently closes after the magnetar spins down and the magnetic pressure drops below ram pressure. The X-ray photons are then trapped behind the merger-nova ejecta until the ejecta becomes optically thin at a later time. This explains the essentially simultaneous re-brightening in both the optical and X-ray light curves. Within this model, future gravitational-wave sources could be associated with a bright X-ray counterpart along with the merger-nova, even if the short GRB jet beams away from Earth

  7. DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically expressed.

    Science.gov (United States)

    Hitchins, Megan P; Bentley, Louise; Monk, David; Beechey, Colin; Peters, Jo; Kelsey, Gavin; Ishino, Fumitoshi; Preece, Michael A; Stanier, Philip; Moore, Gudrun E

    2002-12-01

    Maternal duplication of human 7p11.2-p13 has been associated with Silver-Russell syndrome (SRS) in two familial cases. GRB10 is the only imprinted gene identified within this region to date. GRB10 demonstrates an intricate tissue- and isoform-specific imprinting profile in humans, with paternal expression in fetal brain and maternal expression of one isoform in skeletal muscle. The mouse homolog is maternally transcribed. The GRB10 protein is a potent growth inhibitor and represents a candidate for SRS, which is characterized by pre- and postnatal growth retardation and a spectrum of additional dysmorphic features. Since imprinted genes tend to be grouped in clusters, we investigated the imprinting status of the dopa-decarboxylase gene (DDC) and the Cordon-bleu gene (COBL) which flank GRB10 within the 7p11.2-p13 SRS duplicated region. Although both genes were found to replicate asynchronously, suggestive of imprinting, SNP expression analyses showed that neither gene was imprinted in multiple human fetal tissues. The mouse homologues, Ddc and Cobl, which map to the homologous imprinted region on proximal Chr 11, were also biallelically expressed in mice with uniparental maternal or paternal inheritance of this region. With the intent of using mouse Grb10 as an imprinted control, biallelic expression was consistently observed in fetal, postnatal, and adult brain of these mice, in contrast to the maternal-specific transcription previously demonstrated in brain in inter-specific F1 progeny. This may be a further example of over-expression of maternally derived transcripts in inter-specific mouse crosses. GRB10 remains the only imprinted gene identified within 7p11.2-p13.

  8. The two-component afterglow of Swift GRB 050802

    Science.gov (United States)

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

    2007-09-01

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

  9. A serendipitous observation of the gamma-ray burst GRB 921013b field with EUVE

    DEFF Research Database (Denmark)

    Castro-Tirado, A.J.; Gorosabel, J.; Bowyer, S.

    1999-01-01

    hours after the burst is 1.8 x10(-16) erg s(-1) cm(-2) after correction for absorption by the Galactic interstellar medium. Even if we exclude an intrinsic absorption, this is well below the detection limit of the EUVE measurement. Although it is widely accepted that gamma-ray bursts are at cosmological......We report a serendipitous extreme ultraviolet observation by EUVE of the field containing GRB 921013b, similar to 11 hours after its occurrence. This burst was detected on 1992 October 13 by the WATCH and PHEBUS on Granat, and by the GRB experiment on Ulysses. The lack of any transient (or...

  10. Discovery of the optical counterpart and early optical observations of GRB 990712

    DEFF Research Database (Denmark)

    Sahu, K.C.; Vreesvijk, P.; Bakos, G.

    2000-01-01

    We present the discovery observations of the optical counterpart of the gamma-ray burst GRB 990712 taken 4.16 hr after the outburst and discuss its light curve observed in the V, R, and I bands during the first similar to 35 days after the outburst. The observed light curves were fitted with a po......We present the discovery observations of the optical counterpart of the gamma-ray burst GRB 990712 taken 4.16 hr after the outburst and discuss its light curve observed in the V, R, and I bands during the first similar to 35 days after the outburst. The observed light curves were fitted...

  11. Four Years of Real-Time GRB Followup by BOOTES-1B (2005–2008

    Directory of Open Access Journals (Sweden)

    Martin Jelínek

    2010-01-01

    Full Text Available Four years of BOOTES-1B GRB follow-up history are summarised for the first time in the form of a table. The successfully followed events are described case by case. Further, the data are used to show the GRB trigger rate in Spain on a per-year basis, resulting in an estimate of 18 triggers and about 51 hours of telescope time per year for real-time triggers. These numbers grow to about 22 triggers and 77 hours per year if we include also the GRBs observable within 2 hours after the trigger.

  12. Observation of the prompt and early afterglow of GRB 050904 by TAROT

    International Nuclear Information System (INIS)

    Boeer, M.; Damerdji, Y.; Atteia, J. L.; Stratta, G.; Gendre, B.; Klotz, A.

    2006-01-01

    We present the recent observation of the very high redshift burst source GRB 050904 made by the TAROT robotized telescope. We have compared our data with the SWIFT XRT light curve to analyze the broad ban spectrum. We show that the luminosity and the behavior of this event is comparable with that of GRB 990123, suggesting the existence of very bright events. They can be detected at very high redshifts, even with small or moderate aperture telescopes, and they may constitute a powerful means for the exploration of the young universe. An update of the last TAROT observations performed as a response from SWIFT alerts is made

  13. Optically selected GRB afterglows, a real time analysis system at the CFHT

    International Nuclear Information System (INIS)

    Malacrino, F.; Atteia, J.-L.; Klotz, A.; Boer, M.; Kavelaars, J.J.; Cuillandre, J.-C.

    2005-01-01

    We attempt to detect optical GRB afterglows on images taken by the Canada France Hawaii Telescope for the Very Wide survey, component of the Legacy Survey. To do so, a Real Time Analysis System called Optically Selected GRB Afterglows has been installed on a dedicated computer in Hawaii. This pipeline automatically and quickly analyzes Mega cam images and extracts from them a list of variable objects which is displayed on a web page far validation by a member of the collaboration. The Very Wide survey covers 1200 square degrees down to i 1 = 23.5. This paper briefly explain the RTAS process

  14. Staggering in the cleavage pattern of E. coli ABC-excinuclease

    International Nuclear Information System (INIS)

    Myles, G.M.; Van Houten, B.; Sancar, A.

    1986-01-01

    E. coli ABC excinuclease is a complex of three proteins encoded by the uvrA, uvrB, and uvrC genes. The enzyme repairs DNA mono and diadducts by the single strand cleavage of DNA eight phosphodiester bond 5' and four or five phosphodiester bonds 3' to a DNA lesion and facilitates the removal of the resulting twelve or thirteen nucleotide fragment. In this study, the authors have investigated the excision pattern for ultraviolet (UV) induced diadducts, i.e. cyclobutane pyrimidine dimers and pyrimidine-pyrimidone (6-4) photoproducts. Terminally (5' or 3') labeled DNA was irradiated with 254nm UV and treated with ABC excinuclease before and after photoreactivation of cyclobutane dimers by E. coli DNA photolyase. In this way, the authors were able to differentiate between the cleavage pattern of pyrimidine dimers and of (6-4) photoproducts. Their results show that certain TT cyclobutane dimers and rare TT (6-4) photoproducts are excised by cleavage seven and, less frequently, six phosphodiester bonds to the 5' side of the DNA lesion in addition to the primary cutting site at the eight 5' phosphodiester bond. The 3' cleavage sites are maintained at the fourth and fifth phosphodiester bonds for the these UV induced lesions. These data indicate that the cleavage pattern of the ABC excinuclease may be dependent upon both the type of DNA lesion as well as it surrounding nucleotide sequence. In addition, the authors analysis shows that (6-4) photoproducts are much better substrates for ABC excinuclease than are pyrimidine dimers

  15. The dimer interfaces of protease and extra-protease domains influence the activation of protease and the specificity of GagPol cleavage.

    Science.gov (United States)

    Pettit, Steven C; Gulnik, Sergei; Everitt, Lori; Kaplan, Andrew H

    2003-01-01

    Activation of the human immunodeficiency virus type 1 (HIV-1) protease is an essential step in viral replication. As is the case for all retroviral proteases, enzyme activation requires the formation of protease homodimers. However, little is known about the mechanisms by which retroviral proteases become active within their precursors. Using an in vitro expression system, we have examined the determinants of activation efficiency and the order of cleavage site processing for the protease of HIV-1 within the full-length GagPol precursor. Following activation, initial cleavage occurs between the viral p2 and nucleocapsid proteins. This is followed by cleavage of a novel site located in the transframe domain. Mutational analysis of the dimer interface of the protease produced differential effects on activation and specificity. A subset of mutations produced enhanced cleavage at the amino terminus of the protease, suggesting that, in the wild-type precursor, cleavages that liberate the protease are a relatively late event. Replacement of the proline residue at position 1 of the protease dimer interface resulted in altered cleavage of distal sites and suggests that this residue functions as a cis-directed specificity determinant. In summary, our studies indicate that interactions within the protease dimer interface help determine the order of precursor cleavage and contribute to the formation of extended-protease intermediates. Assembly domains within GagPol outside the protease domain also influence enzyme activation.

  16. Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action.

    Science.gov (United States)

    Deng, Youping; Bhattacharya, Sujoy; Swamy, O Rama; Tandon, Ruchi; Wang, Yong; Janda, Robert; Riedel, Heimo

    2003-10-10

    The regulation of the metabolic insulin response by mouse growth factor receptor-binding protein 10 (Grb10) has been addressed in this report. We find mouse Grb10 to be a critical component of the insulin receptor (IR) signaling complex that provides a functional link between IR and p85 phosphatidylinositol (PI) 3-kinase and regulates PI 3-kinase activity. This regulatory mechanism parallels the established link between IR and p85 via insulin receptor substrate (IRS) proteins. A direct association was demonstrated between Grb10 and p85 but was not observed between Grb10 and IRS proteins. In addition, no effect of mouse Grb10 was observed on the association between IRS-1 and p85, on IRS-1-associated PI 3-kinase activity, or on insulin-mediated activation of IR or IRS proteins. A critical role of mouse Grb10 was observed in the regulation of PI 3-kinase activity and the resulting metabolic insulin response. Dominant-negative Grb10 domains, in particular the SH2 domain, eliminated the metabolic response to insulin in differentiated 3T3-L1 adipocytes. This was consistently observed for glycogen synthesis, glucose and amino acid transport, and lipogenesis. In parallel, the same metabolic responses were substantially elevated by increased levels of Grb10. A similar role of Grb10 was confirmed in mouse L6 cells. In addition to the SH2 domain, the Pro-rich amino-terminal region of Grb10 was implicated in the regulation of PI 3-kinase catalytic activity. These regulatory roles of Grb10 were extended to specific insulin mediators downstream of PI 3-kinase including PKB/Akt, glycogen synthase kinase, and glycogen synthase. In contrast, a regulatory role of Grb10 in parallel insulin response pathways including p70 S6 kinase, ubiquitin ligase Cbl, or mitogen-activated protein kinase p38 was not observed. The dissection of the interaction of mouse Grb10 with p85 and the resulting regulation of PI 3-kinase activity should help elucidate the complexity of the IR signaling

  17. Restriction enzyme cleavage of ultraviolet-damaged Simian virus 40 and pBR322 DNA

    International Nuclear Information System (INIS)

    Cleaver, J.E.

    1983-01-01

    Cleavage of specific DNA sequences by the restriction enzymes EcoRI, HindIII and TaqI was prevented when the DNA was irradiated with ultraviolet light. Most of the effects were attributed to cyclobutane pyrimidine dimers in the recognition sequences; the effectiveness of irradiation was directly proportional to the number of potential dimer sites in the DNA. Combining EcoRI with dimer-specific endonuclease digestion revealed that pyrimidine dimers blocked cleavage within one base-pair on the strand opposite to the dimer but did not block cleavage three to four base-pairs away on the same strand. These are the probable limits for the range of influence of pyrimidine dimers along the DNA, at least for this enzyme. The effect of irradiation on cleavage by TaqI seemed far greater than expected for the cyclobutane dimer yield, possibly because of effects from photoproducts flanking the tetranucleotide recognition sequence and the effect of non-cyclobutane (6-4)pyrimidine photoproducts involving adjacent T and C bases. (author)

  18. Structural and functional basis for RNA cleavage by Ire1

    Directory of Open Access Journals (Sweden)

    Stroud Robert M

    2011-07-01

    Full Text Available Abstract Background The unfolded protein response (UPR controls the protein folding capacity of the endoplasmic reticulum (ER. Central to this signaling pathway is the ER-resident bifunctional transmembrane kinase/endoribonuclease Ire1. The endoribonuclease (RNase domain of Ire1 initiates a non-conventional mRNA splicing reaction, leading to the production of a transcription factor that controls UPR target genes. The mRNA splicing reaction is an obligatory step of Ire1 signaling, yet its mechanism has remained poorly understood due to the absence of substrate-bound crystal structures of Ire1, the lack of structural similarity between Ire1 and other RNases, and a scarcity of quantitative enzymological data. Here, we experimentally define the active site of Ire1 RNase and quantitatively evaluate the contribution of the key active site residues to catalysis. Results This analysis and two new crystal structures suggest that Ire1 RNase uses histidine H1061 and tyrosine Y1043 as the general acid-general base pair contributing ≥ 7.6 kcal/mol and 1.4 kcal/mol to transition state stabilization, respectively, and asparagine N1057 and arginine R1056 for coordination of the scissile phosphate. Investigation of the stem-loop recognition revealed that additionally to the stem-loops derived from the classic Ire1 substrates HAC1 and Xbp1 mRNA, Ire1 can site-specifically and rapidly cleave anticodon stem-loop (ASL of unmodified tRNAPhe, extending known substrate specificity of Ire1 RNase. Conclusions Our data define the catalytic center of Ire1 RNase and suggest a mechanism of RNA cleavage: each RNase monomer apparently contains a separate catalytic apparatus for RNA cleavage, whereas two RNase subunits contribute to RNA stem-loop docking. Conservation of the key residues among Ire1 homologues suggests that the mechanism elucidated here for yeast Ire1 applies to Ire1 in metazoan cells, and to the only known Ire1 homologue RNase L.

  19. Determinants of the VP1/2A junction cleavage by the 3C protease in foot-and-mouth disease virus-infected cells.

    Science.gov (United States)

    Kristensen, Thea; Normann, Preben; Gullberg, Maria; Fahnøe, Ulrik; Polacek, Charlotta; Rasmussen, Thomas Bruun; Belsham, Graham J

    2017-03-01

    The foot-and-mouth disease virus (FMDV) capsid precursor, P1-2A, is cleaved by FMDV 3C protease to yield VP0, VP3, VP1 and 2A. Cleavage of the VP1/2A junction is the slowest. Serotype O FMDVs with uncleaved VP1-2A (having a K210E substitution in VP1; at position P2 in cleavage site) have been described previously and acquired a second site substitution (VP1 E83K) during virus rescue. Furthermore, introduction of the VP1 E83K substitution alone generated a second site change at the VP1/2A junction (2A L2P, position P2' in cleavage site). These virus adaptations have now been analysed using next-generation sequencing to determine sub-consensus level changes in the virus; this revealed other variants within the E83K mutant virus population that changed residue VP1 K210. The construction of serotype A viruses with a blocked VP1/2A cleavage site (containing K210E) has now been achieved. A collection of alternative amino acid substitutions was made at this site, and the properties of the mutant viruses were determined. Only the presence of a positively charged residue at position P2 in the cleavage site permitted efficient cleavage of the VP1/2A junction, consistent with analyses of diverse FMDV genome sequences. Interestingly, in contrast to the serotype O virus results, no second site mutations occurred within the VP1 coding region of serotype A viruses with the blocked VP1/2A cleavage site. However, some of these viruses acquired changes in the 2C protein that is involved in enterovirus morphogenesis. These results have implications for the testing of potential antiviral agents targeting the FMDV 3C protease.

  20. INTEGRAL and XMM-Newton observations of the weak gamma-ray burst GRB 030227

    DEFF Research Database (Denmark)

    Mereghetti, S.; Gotz, D.; Tiengo, A.

    2003-01-01

    We present International Gamma-Ray Astrophysical Laboratory ( INTEGRAL) and XMM-Newton observations of the prompt gamma-ray emission and the X-ray afterglow of GRB 030227, the first gamma-ray burst for which the quick localization obtained with the INTEGRAL Burst Alert System has led...

  1. A novel explosive process is required for the gamma-ray burst GRB 060614.

    Science.gov (United States)

    Gal-Yam, A; Fox, D B; Price, P A; Ofek, E O; Davis, M R; Leonard, D C; Soderberg, A M; Schmidt, B P; Lewis, K M; Peterson, B A; Kulkarni, S R; Berger, E; Cenko, S B; Sari, R; Sharon, K; Frail, D; Moon, D-S; Brown, P J; Cucchiara, A; Harrison, F; Piran, T; Persson, S E; McCarthy, P J; Penprase, B E; Chevalier, R A; MacFadyen, A I

    2006-12-21

    Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required.

  2. Photospheric Emission in the Joint GBM and Konus Prompt Spectra of GRB 120323A

    Energy Technology Data Exchange (ETDEWEB)

    Guiriec, S.; Kouveliotou, C. [Department of Physics, The George Washington University, 725 21st Street NW, Washington, DC 20052 (United States); Gehrels, N.; McEnery, J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Hartmann, D. H., E-mail: sylvain.guiriec@nasa.gov [Department of Physics and Astronomy, Clemson University, Kinard Lab of Physics (United States)

    2017-09-10

    GRB 120323A is a very intense short gamma -ray burst (GRB) detected simultaneously during its prompt γ -ray emission phase with the Gamma-ray Burst Monitor (GBM) on board the Fermi Gamma-ray Space Telescope and the Konus experiment on board the Wind satellite. GBM and Konus operate in the keV–MeV regime; however, the GBM range is broader toward both the low and the high parts of the γ -ray spectrum. Analyses of such bright events provide a unique opportunity to check the consistency of the data analysis as well as cross-calibrate the two instruments. We performed time-integrated and coarse time-resolved spectral analysis of GRB 120323A prompt emission. We conclude that the analyses of GBM and Konus data are only consistent when using a double-hump spectral shape for both data sets; in contrast, the single hump of the empirical Band function, traditionally used to fit GRB prompt emission spectra, leads to significant discrepancies between GBM and Konus analysis results. Our two-hump model is a combination of a thermal-like and a non-thermal component. We interpret the first component as a natural manifestation of the jet photospheric emission.

  3. A tale of two GRB-SNe at a common redshift of z=0.54

    NARCIS (Netherlands)

    Cano, Z.; Bersier, D.; Guidorzi, C.; Margutti, R.; Svensson, K.M.; Kobayashi, S.; Melandri, A.; Wiersema, K.; Pozanenko, A.; van der Horst, A.J.; Pooley, G.G.; Fernandez-Soto, A.; Castro-Tirado, A.J.; de Ugarte Postigo, A.; Im, M.; Kamble, A.P.; Sahu, D.; Alonso-Lorite, J.; Anupama, G.; Bibby, J.L.; Burgdorf, M.J.; Clay, N.; Curran, P.A.; Fatkhullin, T.A.; Fruchter, A.S.; Garnavich, P.; Gomboc, A.; Gorosabel, J.; Graham, J.F.; Gurugubelli, U.; Haislip, J.; Huang, K.; Huxor, A.; Ibrahimov, M.; Jeon, Y.; Jeon, Y.B.; Ivarsen, K.; Kasen, D.; Klunko, E.; Kouveliotou, C.; Lacluyze, A.; Levan, A.J.; Loznikov, V.; Mazzali, P.A.; Moskvitin, A.S.; Mottram, C.; Mundell, C.G.; Nugent, P.E.; Nysewander, M.; O'Brien, P.T.; Park, W.K.; Peris, V.; Pian, E.; Reichart, D.; Rhoads, J.E.; Rol, E.; Rumyantsev, V.; Scowcroft, V.; Shakhovskoy, D.; Small, E.; Smith, R.J.; Sokolov, V.V.; Starling, R.L.C.; Steele, I.; Strom, R.G.; Tanvir, N.R.; Tsapras, Y.; Urata, Y.; Vaduvescu, O.; Volnova, A.; Volvach, A.; Wijers, R.A.M.J.; Woosley, S.E.; Young, D.R.

    2011-01-01

    We present ground-based and Hubble Space Telescope optical observations of the optical transients (OTs) of long-duration Gamma Ray Bursts (GRBs) 060729 and 090618, both at a redshift of z= 0.54. For GRB 060729, bumps are seen in the optical light curves (LCs), and the late-time broad-band spectral

  4. The rapidly flaring afterglow of the very bright and energetic GRB 070125

    NARCIS (Netherlands)

    Updike, A.C.; Haislip, J.B.; Nysewander, M.C.; Fruchter, A.S.; Kann, D.A.; Klose, S.; Milne, P.A.; Williams, G.G.; Zheng, W.; Hergenrother, C.W.; Prochaska, J.X.; Halpern, J.P.; Mirabal, N.; Thorstensen, J.R.; van der Horst, A.J.; Starling, R.L.C.; Racusin, J.L.; Burrows, D.N.; Kuin, N.P.M.; Roming, P.W.A.; Bellm, E.; Hurley, K.; Li, W.; Filippenko, A.V.; Blake, C.; Starr, D.; Falco, E.E.; Brown, W.R.; Dai, X.; Deng, J.; Xin, L.; Qiu, Y.; Wei, J.; Urata, Y.; Nanni, D.; Maiorano, E.; Palazzi, E.; Greco, G.; Bartolini, C.; Guarnieri, A.; Piccioni, A.; Pizzichini, G.; Terra, F.; Misra, K.; Bhatt, B.C.; Anupama, G.C.; Fan, X.; Jiang, L.; Wijers, R.A.M.J.; Reichart, D.E.; Eid, H.A.; Bryngelson, G.; Puls, J.; Goldthwaite, R.C.; Hartmann, D.H.

    2008-01-01

    We report on multiwavelength observations, ranging from X-ray to radio wave bands, of the IPN-localized gamma-ray burst GRB 070125. Spectroscopic observations reveal the presence of absorption lines due to O I, Si II, and C IV, implying a likely redshift of z = 1.547. The well-sampled light curves,

  5. Gamma-ray Burst Formation Environment: Comparison of Redshift Distributions of GRB Afterglows

    Directory of Open Access Journals (Sweden)

    Sung-Eun Kim

    2005-12-01

    Full Text Available Since gamma-ray bursts(GRBs have been first known to science societites in 1973, many scientists are involved in their studies. Observations of GRB afterglows provide us with much information on the environment in which the observed GRBs are born. Study of GRB afterglows deals with longer timescale emissions in lower energy bands (e.g., months or even up to years than prompt emissions in gamma-rays. Not all the bursts accompany afterglows in whole ranges of wavelengths. It has been suggested as a reason for that, for instance, that radio and/or X-ray afterglows are not recorded mainly due to lower sensitivity of detectors, and optical afterglows due to extinctions in intergalactic media or self-extinctions within a host galaxy itself. Based on the idea that these facts may also provide information on the GRB environment, we analyze statistical properties of GRB afterglows. We first select samples of the redshift-known GRBs according to the wavelength of afterglow they accompanied. We then compare their distributions as a function of redshift, using statistical methods. As a results, we find that the distribution of the GRBs with X-ray afterglows is consistent with that of the GRBs with optical afterglows. We, therefore, conclude that the lower detection rate of optical afterglows is not due to extinctions in intergalactic media.

  6. Constraints on the optical afterglow emission of the short/hard burst GRB 010119

    DEFF Research Database (Denmark)

    Gorosabel, J.; Andersen, M.I.; Hjorth, J.

    2002-01-01

    We report optical observations of the short/hard burst GRB 010119 error box, one of the smallest error boxes reported to date for short/hard GRBs. Limits of R >22.3 and I >21.2 are imposed by observations carried out 20.31 and 20.58 hours after the gamma-ray event, respectively. They represent th...

  7. Deep Photometry of GRB 041006 Afterglow: Hypernova Bump at Redshift z = 0.716

    Science.gov (United States)

    Stanek, K. Z.; Garnavich, P. M.; Nutzman, P. A.; Hartman, J. D.; Garg, A.; Adelberger, K.; Berlind, P.; Bonanos, A. Z.; Calkins, M. L.; Challis, P.; Gaudi, B. S.; Holman, M. J.; Kirshner, R. P.; McLeod, B. A.; Osip, D.; Pimenova, T.; Reiprich, T. H.; Romanishin, W.; Spahr, T.; Tegler, S. C.; Zhao, X.

    2005-06-01

    We present deep optical photometry of the afterglow of gamma-ray burst (GRB) 041006 and its associated hypernova obtained over 65 days after detection (55 R-band epochs on 10 different nights). Our early data (tVatican Advanced Technology Telescope, the Magellan 6.5 m Baade and Clay telescopes, and the Keck II 10 m telescope.

  8. Limits on optical polarization duringt the prompt phase of GRB 140430a

    Czech Academy of Sciences Publication Activity Database

    Kopač, D.; Mundell, C. G.; Japelj, J.; Arnold, D. M.; Steele, I.A.; Guidorzi, C.; Dichiara, S.; Kobayashi, S.; Gomboc, A.; Harrison, R. M.; Lamb, G. P.; Melandri, A.; Smith, R. J.; Virgili, F. J.; Castro-Tirado, A.J.; Gorosabel, J.; Järvinen, A.; Sánchez-Ramírez, R.; Oates, S.R.; Jelínek, Martin

    2015-01-01

    Roč. 813, č. 1 (2015), 1/1-1/14 ISSN 0004-637X Institutional support: RVO:67985815 Keywords : gamma-ray burst * GRB 140430A * polarimeters Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 5.909, year: 2015

  9. Very high column density and small reddening toward GRB 020124 at z=3.20

    DEFF Research Database (Denmark)

    Hjorth, J.; Møller, Per; Gorosabel, J.

    2003-01-01

    We present optical and near-infrared observations of the dim afterglow of GRB 020124, obtained between 2 and 68 hr after the gamma-ray burst. The burst occurred in a very faint (Rgreater than or similar to29.5) damped Lyalpha absorber (DLA) at a redshift of z=3.198+/-0.004. The derived column...

  10. The redshift and afterglow of the extremely energetic gamma-ray burst GRB 080916C

    CERN Document Server

    Greiner, J.; Kruehler, T.; Kienlin, A.v.; Rau, A.; Sari, R.; Fox, Derek B.; Kawai, N.; Afonso, P.; Ajello, M.; Berger, E.; Cenko, S.B.; Cucchiara, A.; Filgas, R.; Klose, S.; Yoldas, A.Kuepue; Lichti, G.G.; Loew, S.; McBreen, S.; Nagayama, T.; Rossi, A.; Sato, S.; Szokoly, G.; Yoldas, A.; Zhang, X.-L.

    2009-01-01

    The detection of GeV photons from gamma-ray bursts (GRBs) has important consequences for the interpretation and modelling of these most-energetic cosmological explosions. The full exploitation of the high-energy measurements relies, however, on the accurate knowledge of the distance to the events. Here we report on the discovery of the afterglow and subsequent redshift determination of GRB 080916C, the first GRB detected by the Fermi Gamma-Ray Space Telescope with high significance detection of photons at >0.1 GeV. Observations were done with 7-channel imager GROND at the 2.2m MPI/ESO telescope, the SIRIUS instrument at the Nagoya-SAAO 1.4m telescope in South Africa, and the GMOS instrument at Gemini-S. The afterglow photometric redshift of z=4.35+-0.15, based on simultaneous 7-filter observations with the Gamma-Ray Optical and Near-infrared Detector (GROND), places GRB 080916C among the top 5% most distant GRBs, and makes it the most energetic GRB known to date. The detection of GeV photons from such a dista...

  11. FERMI OBSERVATIONS OF HIGH-ENERGY GAMMA-RAY EMISSION FROM GRB 090217A

    International Nuclear Information System (INIS)

    Ackermann, M.; Ajello, M.; Bechtol, K.; Berenji, B.; Blandford, R. D.; Borgland, A. W.; Bouvier, A.; Baldini, L.; Bellazzini, R.; Bregeon, J.; Brez, A.; Ballet, J.; Barbiellini, G.; Baring, M. G.; Bastieri, D.; Bhat, P. N.; Briggs, M. S.; Bissaldi, E.; Bonamente, E.; Brigida, M.

    2010-01-01

    The Fermi observatory is advancing our knowledge of gamma-ray bursts (GRBs) through pioneering observations at high energies, covering more than seven decades in energy with the two on-board detectors, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). Here, we report on the observation of the long GRB 090217A which triggered the GBM and has been detected by the LAT with a significance greater than 9σ. We present the GBM and LAT observations and on-ground analyses, including the time-resolved spectra and the study of the temporal profile from 8 keV up to ∼1 GeV. All spectra are well reproduced by a Band model. We compare these observations to the first two LAT-detected, long bursts GRB 080825C and GRB 080916C. These bursts were found to have time-dependent spectra and exhibited a delayed onset of the high-energy emission, which are not observed in the case of GRB 090217A. We discuss some theoretical implications for the high-energy emission of GRBs.

  12. Preliminary Results on VLT K-band Imaging Observations of GRB ...

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    E. Le Floc'h, I. F. Mirabel & P.-A. Duc Service d'Astrophysique, CEA-Saclay, ... internal extinction by dust in several GRB hosts has probably led to under- .... We acknowledge our referee for his/her comments which improved the quality of the.

  13. GRB060206 and the quandary of achromatic breaks in afterglow light curves

    NARCIS (Netherlands)

    Curran, P.A.; van der Horst, A.J.; Wijers, R.A.M.J.; Starling, R.L.C.; Castro-Tirado, A.J.; Fynbo, J.P.U.; Gorosabel, J.; Järvinen, A.S.; Malesani, D.; Rol, E.; Tanvir, N.R.; Wiersema, K.; Burleigh, M.R.; Casewell, S.L.; Dobbie, P.D.; Guziy, S.; Jakobsson, P.; Jelínek, M.; Laursen, P.; Levan, A.J.; Mundell, C.G.; Näränen, J.; Piranomonte, S.

    2007-01-01

    Gamma-ray burst afterglow observations in the Swift era have a perceived lack of achromatic jet breaks compared with the BeppoSAX era. We present our multi-wavelength analysis of GRB060206 as an illustrative example of how inferences of jet breaks from optical and X-ray data might differ. The

  14. The origin of the early-time optical emission of Swift GRB 080310

    NARCIS (Netherlands)

    Littlejohns, O.M.; Willingale, R.; O'Brien, P.T.; Beardmore, A.P.; Covino, S.; Perley, D.A.; Tanvir, N.R.; Rol, E.; Yuan, F.; Akerlof, C.; D'Avanzo, P.; Bersier, D.F.; Castro-Tirado, A.J.; Christian, P.; Cobb, B.E.; Evans, P.A.; Filippenko, A.V.; Flewelling, H.; Fugazza, D.; Hoversten, E.A.; Kamble, A.P.; Kobayashi, S.; Li, W.; Morgan, A.N.; Mundell, C.G.; Page, K.; Palazzi, E.; Quimby, R.M.; Schulze, S.; Steele, I.A.; de Ugarte Postigo, A.

    2012-01-01

    We present broad-band multiwavelength observations of GRB 080310 at redshift z= 2.43. This burst was bright and long-lived, and unusual in having extensive optical and near-infrared (IR) follow-up during the prompt phase. Using these data we attempt to simultaneously model the gamma-ray, X-ray,

  15. SPECTROSCOPIC EVIDENCE FOR SN 2010ma ASSOCIATED WITH GRB 101219B

    International Nuclear Information System (INIS)

    Sparre, M.; Fynbo, J. P. U.; Malesani, D.; De Ugarte Postigo, A.; Hjorth, J.; Leloudas, G.; Milvang-Jensen, B.; Watson, D. J.; Sollerman, J.; Goldoni, P.; Covino, S.; Tagliaferri, G.; D'Elia, V.; Flores, H.; Hammer, F.; Jakobsson, P.; Schulze, S.; Kaper, L.; Levan, A. J.; Tanvir, N. R.

    2011-01-01

    We report on the spectroscopic detection of supernova SN 2010ma associated with the long gamma-ray burst GRB 101219B. We observed the optical counterpart of the GRB on three nights with the X-shooter spectrograph at the Very Large Telescope. From weak absorption lines, we measure a redshift of z = 0.55. The first-epoch UV-near-infrared afterglow spectrum, taken 11.6 hr after the burst, is well fit by a power law consistent with the slope of the X-ray spectrum. The second- and third-epoch spectra (obtained 16.4 and 36.7 days after the burst), however, display clear bumps closely resembling those of the broad-lined type-Ic SN 1998bw if placed at z = 0.55. Apart from demonstrating that spectroscopic SN signatures can be observed for GRBs at these large distances, our discovery makes a step forward in establishing a general connection between GRBs and SNe. In fact, unlike most previous unambiguous GRB-associated SNe, GRB 101219B has a large gamma-ray energy (E iso = 4.2 x 10 51 erg), a bright afterglow, and obeys the 'Amati' relation, thus being fully consistent with the cosmological population of GRBs.

  16. Full Length Research Paper Curcumin induces cleavage of -catenin ...

    African Journals Online (AJOL)

    β-Catenin/Tcf-4 signaling pathway plays important roles in colorectal tumorigenesis. RT-PCR, western blotting and immunoprecipitation were used to study the effects of curcumin on β-catenin/Tcf-4 signaling pathway in HT-29 cells. Treatment of curcumin could induce cleavage of β-catenin and the cleavage could be ...

  17. Modeling and inferring cleavage patterns in proliferating epithelia.

    Directory of Open Access Journals (Sweden)

    Ankit B Patel

    2009-06-01

    Full Text Available The regulation of cleavage plane orientation is one of the key mechanisms driving epithelial morphogenesis. Still, many aspects of the relationship between local cleavage patterns and tissue-level properties remain poorly understood. Here we develop a topological model that simulates the dynamics of a 2D proliferating epithelium from generation to generation, enabling the exploration of a wide variety of biologically plausible cleavage patterns. We investigate a spectrum of models that incorporate the spatial impact of neighboring cells and the temporal influence of parent cells on the choice of cleavage plane. Our findings show that cleavage patterns generate "signature" equilibrium distributions of polygonal cell shapes. These signatures enable the inference of local cleavage parameters such as neighbor impact, maternal influence, and division symmetry from global observations of the distribution of cell shape. Applying these insights to the proliferating epithelia of five diverse organisms, we find that strong division symmetry and moderate neighbor/maternal influence are required to reproduce the predominance of hexagonal cells and low variability in cell shape seen empirically. Furthermore, we present two distinct cleavage pattern models, one stochastic and one deterministic, that can reproduce the empirical distribution of cell shapes. Although the proliferating epithelia of the five diverse organisms show a highly conserved cell shape distribution, there are multiple plausible cleavage patterns that can generate this distribution, and experimental evidence suggests that indeed plants and fruitflies use distinct division mechanisms.

  18. The Generation of Dehydroalanine Residues in Protonated Polypeptides: Ion/Ion Reactions for Introducing Selective Cleavages

    Science.gov (United States)

    Peng, Zhou; Bu, Jiexun; McLuckey, Scott A.

    2017-09-01

    We examine a gas-phase approach for converting a subset of amino acid residues in polypeptide cations to dehydroalanine (Dha). Subsequent activation of the modified polypeptide ions gives rise to specific cleavage N-terminal to the Dha residue. This process allows for the incorporation of selective cleavages in the structural characterization of polypeptide ions. An ion/ion reaction within the mass spectrometer between a multiply protonated polypeptide and the sulfate radical anion introduces a radical site into the multiply protonated polypeptide reactant. Subsequent collisional activation of the polypeptide radical cation gives rise to radical side chain loss from one of several particular amino acid side chains (e.g., leucine, asparagine, lysine, glutamine, and glutamic acid) to yield a Dha residue. The Dha residues facilitate preferential backbone cleavages to produce signature c- and z-ions, demonstrated with cations derived from melittin, mechano growth factor (MGF), and ubiquitin. The efficiencies for radical side chain loss and for subsequent generation of specific c- and z-ions have been examined as functions of precursor ion charge state and activation conditions using cations of ubiquitin as a model for a small protein. It is noted that these efficiencies are not strongly dependent on ion trap collisional activation conditions but are sensitive to precursor ion charge state. Moderate to low charge states show the greatest overall yields for the specific Dha cleavages, whereas small molecule losses (e.g., water/ammonia) dominate at the lowest charge states and proton catalyzed amide bond cleavages that give rise to b- and y-ions tend to dominate at high charge states. [Figure not available: see fulltext.

  19. Maximizing Selective Cleavages at Aspartic Acid and Proline Residues for the Identification of Intact Proteins

    Science.gov (United States)

    Foreman, David J.; Dziekonski, Eric T.; McLuckey, Scott A.

    2018-04-01

    A new approach for the identification of intact proteins has been developed that relies on the generation of relatively few abundant products from specific cleavage sites. This strategy is intended to complement standard approaches that seek to generate many fragments relatively non-selectively. Specifically, this strategy seeks to maximize selective cleavage at aspartic acid and proline residues via collisional activation of precursor ions formed via electrospray ionization (ESI) under denaturing conditions. A statistical analysis of the SWISS-PROT database was used to predict the number of arginine residues for a given intact protein mass and predict a m/z range where the protein carries a similar charge to the number of arginine residues thereby enhancing cleavage at aspartic acid residues by limiting proton mobility. Cleavage at aspartic acid residues is predicted to be most favorable in the m/z range of 1500-2500, a range higher than that normally generated by ESI at low pH. Gas-phase proton transfer ion/ion reactions are therefore used for precursor ion concentration from relatively high charge states followed by ion isolation and subsequent generation of precursor ions within the optimal m/z range via a second proton transfer reaction step. It is shown that the majority of product ion abundance is concentrated into cleavages C-terminal to aspartic acid residues and N-terminal to proline residues for ions generated by this process. Implementation of a scoring system that weights both ion fragment type and ion fragment area demonstrated identification of standard proteins, ranging in mass from 8.5 to 29.0 kDa. [Figure not available: see fulltext.

  20. Modeling The GRB Host Galaxy Mass Distribution: Are GRBs Unbiased Tracers of Star Formation?

    Energy Technology Data Exchange (ETDEWEB)

    Kocevski, Daniel; /KIPAC, Menlo Park; West, Andrew A.; /UC, Berkeley, Astron. Dept. /MIT, MKI; Modjaz, Maryam; /UC, Berkeley, Astron. Dept.

    2009-08-03

    We model the mass distribution of long gamma-ray burst (GRB) host galaxies given recent results suggesting that GRBs occur in low metallicity environments. By utilizing measurements of the redshift evolution of the mass-metallicity (M-Z) relationship for galaxies, along with a sharp host metallicity cut-off suggested by Modjaz and collaborators, we estimate an upper limit on the stellar mass of a galaxy that can efficiently produce a GRB as a function of redshift. By employing consistent abundance indicators, we find that sub-solar metallicity cut-offs effectively limit GRBs to low stellar mass spirals and dwarf galaxies at low redshift. At higher redshifts, as the average metallicity of galaxies in the Universe falls, the mass range of galaxies capable of hosting a GRB broadens, with an upper bound approaching the mass of even the largest spiral galaxies. We compare these predicted limits to the growing number of published GRB host masses and find that extremely low metallicity cut-offs of 0.1 to 0.5 Z{sub {circle_dot}} are effectively ruled out by a large number of intermediate mass galaxies at low redshift. A mass function that includes a smooth decrease in the efficiency of producing GRBs in galaxies of metallicity above 12+log(O/H){sub KK04} = 8.7 can, however, accommodate a majority of the measured host galaxy masses. We find that at z {approx} 1, the peak in the observed GRB host mass distribution is inconsistent with the expected peak in the mass of galaxies harboring most of the star formation. This suggests that GRBs are metallicity biased tracers of star formation at low and intermediate redshifts, although our model predicts that this bias should disappear at higher redshifts due to the evolving metallicity content of the universe.

  1. MODELING THE GRB HOST GALAXY MASS DISTRIBUTION: ARE GRBs UNBIASED TRACERS OF STAR FORMATION?

    International Nuclear Information System (INIS)

    Kocevski, Daniel; West, Andrew A.; Modjaz, Maryam

    2009-01-01

    We model the mass distribution of long gamma-ray burst (GRB) host galaxies given recent results suggesting that GRBs occur in low-metallicity environments. By utilizing measurements of the redshift evolution of the mass-metallicity relationship for galaxies, along with a sharp host metallicity cutoff suggested by Modjaz and collaborators, we estimate an upper limit on the stellar mass of a galaxy that can efficiently produce a GRB as a function of redshift. By employing consistent abundance indicators, we find that subsolar metallicity cutoffs effectively limit GRBs to low-stellar mass spirals and dwarf galaxies at low redshift. At higher redshifts, as the average metallicity of galaxies in the Universe falls, the mass range of galaxies capable of hosting a GRB broadens, with an upper bound approaching the mass of even the largest spiral galaxies. We compare these predicted limits to the growing number of published GRB host masses and find that extremely low-metallicity cutoffs of 0.1 to 0.5 Z sun are effectively ruled out by a large number of intermediate mass galaxies at low redshift. A mass function that includes a smooth decrease in the efficiency of producing GRBs in galaxies of metallicity above 12+log(O/H) KK04 = 8.7 can, however, accommodate a majority of the measured host galaxy masses. We find that at z ∼ 1, the peak in the observed GRB host mass distribution is inconsistent with the expected peak in the mass of galaxies harboring most of the star formation. This suggests that GRBs are metallicity-biased tracers of star formation at low and intermediate redshifts, although our model predicts that this bias should disappear at higher redshifts due to the evolving metallicity content of the universe.

  2. HIGH-ENERGY EMISSION OF GRB 130427A: EVIDENCE FOR INVERSE COMPTON RADIATION

    International Nuclear Information System (INIS)

    Fan, Yi-Zhong; Zhang, Fu-Wen; He, Hao-Ning; Zhou, Bei; Yang, Rui-Zhi; Jin, Zhi-Ping; Wei, Da-Ming; Tam, P. H. T.; Liang, Yun-Feng

    2013-01-01

    A nearby superluminous burst GRB 130427A was simultaneously detected by six γ-ray space telescopes (Swift, the Fermi GLAST Burst Monitor (GBM)/Large Area Telescope, Konus-Wind, SPI-ACS/INTEGRAL, AGILE, and RHESSI) and by three RAPTOR full-sky persistent monitors. The isotropic γ-ray energy release is ∼10 54 erg, rendering it the most powerful explosion among gamma-ray bursts (GRBs) with a redshift z ≤ 0.5. The emission above 100 MeV lasted about one day, and four photons are at energies greater than 40 GeV. We show that the count rate of 100 MeV-100 GeV emission may be mainly accounted for by the forward shock synchrotron radiation and the inverse Compton radiation likely dominates at GeV-TeV energies. In particular, an inverse Compton radiation origin is favored for the ∼(95.3, 47.3, 41.4, 38.5, 32) GeV photons arriving at t ∼ (243, 256.3, 610.6, 3409.8, 34366.2) s after the trigger of Fermi-GBM. Interestingly, the external inverse Compton scattering of the prompt emission (the second episode, i.e., t ∼ 120-260 s) by the forward-shock-accelerated electrons is expected to produce a few γ-rays at energies above 10 GeV, while five were detected in the same time interval. A possible unified model for the prompt soft γ-ray, optical, and GeV emission of GRB 130427A, GRB 080319B, and GRB 090902B is outlined. Implications of the null detection of >1 TeV neutrinos from GRB 130427A by IceCube are discussed

  3. A molecular gas-rich GRB host galaxy at the peak of cosmic star formation

    Science.gov (United States)

    Arabsalmani, M.; Le Floc'h, E.; Dannerbauer, H.; Feruglio, C.; Daddi, E.; Ciesla, L.; Charmandaris, V.; Japelj, J.; Vergani, S. D.; Duc, P.-A.; Basa, S.; Bournaud, F.; Elbaz, D.

    2018-05-01

    We report the detection of the CO(3-2) emission line from the host galaxy of gamma-ray burst (GRB) 080207 at z = 2.086. This is the first detection of molecular gas in emission from a GRB host galaxy beyond redshift 1. We find this galaxy to be rich in molecular gas with a mass of 1.1 × 10^{11} M_{{\\odot }} assuming αCO = 4.36 M_{{\\odot }} (K km s^{-1} pc^2)^{-1}. The molecular gas mass fraction of the galaxy is ˜0.5, typical of star-forming galaxies (SFGs) with similar stellar masses and redshifts. With an SFR_{FIR} of 260 M_{{\\odot }} yr^{-1}, we measure a molecular gas depletion time-scale of 0.43 Gyr, near the peak of the depletion time-scale distribution of SFGs at similar redshifts. Our findings are therefore in contradiction with the proposed molecular gas deficiency in GRB host galaxies. We argue that the reported molecular gas deficiency for GRB hosts could be the artefact of improper comparisons or neglecting the effect of the typical low metallicities of GRB hosts on the CO-to-molecular-gas conversion factor. We also compare the kinematics of the CO(3-2) emission line to that of the H α emission line from the host galaxy. We find the H α emission to have contributions from two separate components, a narrow and a broad one. The narrow component matches the CO emission well in velocity space. The broad component, with a full width at half-maximum of ˜1100 km s^{-1}, is separated by +390 km s^{-1} in velocity space from the narrow component. We speculate this broad component to be associated with a powerful outflow in the host galaxy or in an interacting system.

  4. Afterglow Imaging and Polarization of Misaligned Structured GRB Jets and Cocoons: Breaking the Degeneracy in GRB 170817A

    Science.gov (United States)

    Gill, Ramandeep; Granot, Jonathan

    2018-05-01

    The X-ray to radio afterglow emission of GRB 170817A / GW 170817 so far scales as Fν∝ν-0.6t0.8 with observed frequency and time, consistent with a single power-law segment of the synchrotron spectrum from the external shock going into the ambient medium. This requires the effective isotropic equivalent afterglow shock energy in the visible region to increase as ˜t1.7. The two main channels for such an energy increase are (i) radial: more energy carried by slower material (in the visible region) gradually catches up with the afterglow shock and energizes it, and (ii) angular: more energy in relativistic outflow moving at different angles to our line of sight, whose radiation is initially beamed away from us but its beaming cone gradually reaches our line of sight as it decelerates. One cannot distinguish between these explanations (or combinations of them) using only the X-ray to radio Fν(t). Here we demonstrate that the most promising way to break this degeneracy is through afterglow imaging and polarization, by calculating the predicted evolution of the afterglow image (its size, shape and flux centroid) and linear polarization Π(t) for different angular and/or radial outflow structures that fit Fν(t). We consider two angular profiles - a Gaussian and a narrow core with power-law wings in energy per solid angle, as well as a (cocoon motivated) (quasi-) spherical flow with radial velocity profile. For a jet viewed off-axis (and a magnetic field produced in the afterglow shock) Π(t) peaks when the jet's core becomes visible, at ≈2tp where the lightcurve peaks at tp, and the image can be elongated with aspect ratios ≳ 2. A quasi-spherical flow has an almost circular image and a much lower Π(t) (peaking at ≈tp) and flux centroid displacement θfc (a spherical flow has Π(t) = θfc = 0 and a perfectly circular image).

  5. Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO.

    Science.gov (United States)

    Zhu, Xinyu; Fang, Liurong; Wang, Dang; Yang, Yuting; Chen, Jiyao; Ye, Xu; Foda, Mohamed Frahat; Xiao, Shaobo

    2017-02-01

    Porcine deltacoronavirus (PDCoV) causes acute enteric disease and mortality in seronegative neonatal piglets. Previously we have demonstrated that PDCoV infection suppresses the production of interferon-beta (IFN-β), while the detailed mechanisms are poorly understood. Here, we demonstrate that nonstructural protein 5 (nsp5) of PDCoV, the 3C-like protease, significantly inhibits Sendai virus (SEV)-induced IFN-β production by targeting the NF-κB essential modulator (NEMO), confirmed by the diminished function of NEMO cleaved by PDCoV. The PDCoV nsp5 cleavage site in the NEMO protein was identified as glutamine 231, and was identical to the porcine epidemic diarrhea virus nsp5 cleavage site, revealing the likelihood of a common target in NEMO for coronaviruses. Furthermore, this cleavage impaired the ability of NEMO to activate the IFN response and downstream signaling. Taken together, our findings reveal PDCoV nsp5 to be a newly identified IFN antagonist and enhance the understanding of immune evasion by deltacoronaviruses. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Quantification of DNA cleavage specificity in Hi-C experiments.

    Science.gov (United States)

    Meluzzi, Dario; Arya, Gaurav

    2016-01-08

    Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to deduce genomewide interactions between arbitrary loci. A key step in these experiments is the cleavage of cross-linked chromatin with a restriction endonuclease. Although this cleavage should happen specifically at the enzyme's recognition sequence, an unknown proportion of cleavage events may involve other sequences, owing to the enzyme's star activity or to random DNA breakage. A quantitative estimation of these non-specific cleavages may enable simulating realistic Hi-C read pairs for validation of downstream analyses, monitoring the reproducibility of experimental conditions and investigating biophysical properties that correlate with DNA cleavage patterns. Here we describe a computational method for analyzing Hi-C read pairs to estimate the fractions of cleavages at different possible targets. The method relies on expressing an observed local target distribution downstream of aligned reads as a linear combination of known conditional local target distributions. We validated this method using Hi-C read pairs obtained by computer simulation. Application of the method to experimental Hi-C datasets from murine cells revealed interesting similarities and differences in patterns of cleavage across the various experiments considered. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. IDENTIFYING THE LOCATION IN THE HOST GALAXY OF THE SHORT GRB 111117A WITH THE CHANDRA SUBARCSECOND POSITION

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, T.; Troja, E. [Center for Research and Exploration in Space Science and Technology (CRESST), NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Aoki, K. [Subaru Telescope, National Astronomical Observatory of Japan, 650 North A' ohoku Place, Hilo, HI 96720 (United States); Guiriec, S.; Barthelmy, S. D. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Im, M.; Jeon, Y. [Center for the Exploration of the Origin of the Universe (CEOU), Department of Physics and Astronomy, Seoul National University, Seoul, 151-747 (Korea, Republic of); Leloudas, G.; Malesani, D.; De Ugarte Postigo, A.; Andersen, M. I. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen O (Denmark); Melandri, A.; D' Avanzo, P. [INAF-Osservatorio Astronomico di Brera, via Bianchi 46, I-23807 Merate (Italy); Urata, Y. [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Xu, D. [Department of Particle Physics and Astronomy, The Weizmann Institute of Science, Rehovot 76100 (Israel); Gorosabel, J.; Sanchez-Ramirez, R. [Instituto de Astrofisica de Andalucia (CSIC), Glorieta de la Astronomia s/n, E-18008 Granada (Spain); Bai, J. [Yunnan Astronomical Observatory, Chinese Academy of Sciences, Kunming, Yunnan Province, 650011 (China); Briggs, M. S. [Center for Space Plasma and Aeronomic Research, University of Alabama in Huntsville, 320 Sparkman Drive, Huntsville, AL 35805 (United States); Foley, S. [Max-Planck-Institut fuer extraterrestrische Physik, Giessenbachstrasse 1, D-85748 Garching (Germany); and others

    2013-03-20

    We present our successful Chandra program designed to identify, with subarcsecond accuracy, the X-ray afterglow of the short GRB 111117A, which was discovered by Swift and Fermi. Thanks to our rapid target of opportunity request, Chandra clearly detected the X-ray afterglow, though no optical afterglow was found in deep optical observations. The host galaxy was clearly detected in the optical and near-infrared band, with the best photometric redshift of z=1.31{sub -0.23}{sup +0.46} (90% confidence), making it one of the highest known short gamma-ray burst (GRB) redshifts. Furthermore, we see an offset of 1.0 {+-} 0.2 arcsec, which corresponds to 8.4 {+-} 1.7 kpc, between the host and the afterglow position. We discuss the importance of using Chandra for obtaining subarcsecond X-ray localizations of short GRB afterglows to study GRB environments.

  8. An Ordinary Short Gamma-Ray Burst with Extraordinary Implications: Fermi -GBM Detection of GRB 170817A

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, A.; Roberts, O. J.; Connaughton, V. [Science and Technology Institute, Universities Space Research Association, Huntsville, AL 35805 (United States); Veres, P.; Briggs, M. S.; Hamburg, R.; Preece, R. D.; Poolakkil, S. [Center for Space Plasma and Aeronomic Research, University of Alabama in Huntsville, 320 Sparkman Drive, Huntsville, AL 35899 (United States); Burns, E.; Racusin, J.; Canton, T. Dal [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Kocevski, D.; Wilson-Hodge, C. A.; Hui, C. M.; Littenberg, T. [Astrophysics Office, ST12, NASA/Marshall Space Flight Center, Huntsville, AL 35812 (United States); Kienlin, A. von [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse 1, D-85748 Garching (Germany); Christensen, N.; Broida, J. [Physics and Astronomy, Carleton College, MN 55057 (United States); Siellez, K. [Center for Relativistic Astrophysics and School of Physics, Georgia Institute of Technology, Atlanta, GA 30332 (United States); Blackburn, L., E-mail: Adam.M.Goldstein@nasa.gov [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); and others

    2017-10-20

    On 2017 August 17 at 12:41:06 UTC the Fermi Gamma-ray Burst Monitor (GBM) detected and triggered on the short gamma-ray burst (GRB) 170817A. Approximately 1.7 s prior to this GRB, the Laser Interferometer Gravitational-wave Observatory triggered on a binary compact merger candidate associated with the GRB. This is the first unambiguous coincident observation of gravitational waves and electromagnetic radiation from a single astrophysical source and marks the start of gravitational-wave multi-messenger astronomy. We report the GBM observations and analysis of this ordinary short GRB, which extraordinarily confirms that at least some short GRBs are produced by binary compact mergers.

  9. An optical study of the GRB 970111 field beginning 19 hours after the gamma-ray burst

    DEFF Research Database (Denmark)

    Gorosabel, J.; Castro-Tirado, A.J.; Wolf, Christian

    1998-01-01

    to estimate photometric redshifts in the range 0.2 4 for several galaxies in this field and we did not find any conspicuous unusual object. We note that GRB 970111 and GRB 980329 could belong to the same class of GRBs, which may be related to nearby sources (2 similar to 1) in which high intrinsic...... with B galaxy with redshift z = 0.657, which we propose as the optical counterpart of the X-ray source. Further observations allowed to perform...... multicolour photometry for objects in the GRB 970111 error box. The colour-colour diagrams do not show any object with unusual colours. We applied a photometric classification method to the objects inside the GRB error box, that can distinguish stars from galaxies and estimate redshifts. We were able...

  10. Receptor tyrosine phosphatase R-PTP-alpha is tyrosine-phosphorylated and associated with the adaptor protein Grb2

    DEFF Research Database (Denmark)

    Su, J; Batzer, A; Sap, J

    1994-01-01

    Receptor tyrosine phosphatases (R-PTPases) have generated interest because of their suspected involvement in cellular signal transduction. The adaptor protein Grb2 has been implicated in coupling receptor tyrosine kinases to Ras. We report that a ubiquitous R-PTPase, R-PTP-alpha, is tyrosine......-phosphorylated and associated in vivo with the Grb2 protein. This association can be reproduced in stably and transiently transfected cells, as well as in vitro using recombinant Grb2 protein. Association requires the presence of an intact SH2 domain in Grb2, as well as tyrosine phosphorylation of R-PTP-alpha. This observation...... links a receptor tyrosine phosphatase with a key component of a central cellular signalling pathway and provides a basis for addressing R-PTP-alpha function....

  11. Adaptor protein GRB2 promotes Src tyrosine kinase activation and podosomal organization by protein-tyrosine phosphatase ϵ in osteoclasts.

    Science.gov (United States)

    Levy-Apter, Einat; Finkelshtein, Eynat; Vemulapalli, Vidyasiri; Li, Shawn S-C; Bedford, Mark T; Elson, Ari

    2014-12-26

    The non-receptor isoform of protein-tyrosine phosphatase ϵ (cyt-PTPe) supports adhesion of bone-resorbing osteoclasts by activating Src downstream of integrins. Loss of cyt-PTPe reduces Src activity in osteoclasts, reduces resorption of mineralized matrix both in vivo and in cell culture, and induces mild osteopetrosis in young female PTPe KO mice. Activation of Src by cyt-PTPe is dependent upon this phosphatase undergoing phosphorylation at its C-terminal Tyr-638 by partially active Src. To understand how cyt-PTPe activates Src, we screened 73 Src homology 2 (SH2) domains for binding to Tyr(P)-638 of cyt-PTPe. The SH2 domain of GRB2 bound Tyr(P)-638 of cyt-PTPe most prominently, whereas the Src SH2 domain did not bind at all, suggesting that GRB2 may link PTPe with downstream molecules. Further studies indicated that GRB2 is required for activation of Src by cyt-PTPe in osteoclast-like cells (OCLs) in culture. Overexpression of GRB2 in OCLs increased activating phosphorylation of Src at Tyr-416 and of cyt-PTPe at Tyr-638; opposite results were obtained when GRB2 expression was reduced by shRNA or by gene inactivation. Phosphorylation of cyt-PTPe at Tyr-683 and its association with GRB2 are integrin-driven processes in OCLs, and cyt-PTPe undergoes autodephosphorylation at Tyr-683, thus limiting Src activation by integrins. Reduced GRB2 expression also reduced the ability of bone marrow precursors to differentiate into OCLs and reduced the fraction of OCLs in which podosomal adhesion structures assume organization typical of active, resorbing cells. We conclude that GRB2 physically links cyt-PTPe with Src and enables cyt-PTPe to activate Src downstream of activated integrins in OCLs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Search for GRB related prompt optical emission and other fast varying objects with ``Pi of the Sky'' detector

    Science.gov (United States)

    Ćwiok, M.; Dominik, W.; Małek, K.; Mankiewicz, L.; Mrowca-Ciułacz, J.; Nawrocki, K.; Piotrowski, L. W.; Sitek, P.; Sokołowski, M.; Wrochna, G.; Żarnecki, A. F.

    2007-06-01

    Experiment “Pi of the Sky” is designed to search for prompt optical emission from GRB sources. 32 CCD cameras covering 2 steradians will monitor the sky continuously. The data will be analysed on-line in search for optical flashes. The prototype with 2 cameras operated at Las Campanas (Chile) since 2004 has recognised several outbursts of flaring stars and has given limits for a few GRB.

  13. miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

    International Nuclear Information System (INIS)

    Zhang, Yunda; Xu, Guoxing; Liu, Gang; Ye, Yongzhi; Zhang, Chuankai; Fan, Chuannan; Wang, Haibin; Cai, Huali; Xiao, Rui; Huang, Zhengjie; Luo, Qi

    2016-01-01

    miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2 is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.

  14. miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yunda [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 (China); Xu, Guoxing [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 (China); Liu, Gang; Ye, Yongzhi [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Zhang, Chuankai [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 (China); Fan, Chuannan [State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361102 (China); Wang, Haibin; Cai, Huali; Xiao, Rui [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 (China); Huang, Zhengjie, E-mail: huangzhengjie@xmu.edu.cn [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 (China); Luo, Qi, E-mail: luoqixmzsh@126.com [Department of Gastrointestinal Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361003 (China); Department of Gastrointestinal Surgery, First Clinical Medical College of Fujian Medical University, Fuzhou 350005 (China)

    2016-08-05

    miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. - Highlights: • miR-411-5p is downregulated in breast cancer tissues and cell lines. • miR-411-5p inhibits breast cancer cells growth, migration and invasion in vitro. • GRB2 is a direct target of miR-411-5p in breast cancer. • GRB2 is overexpressed in breast cancer and associates with disease outcome. • miR-411-5p suppresses breast cancer progression though GRB2-SOS-Ras pathway.

  15. Cleavage/alteration of interleukin-8 by matrix metalloproteinase-9 in the female lower genital tract.

    Science.gov (United States)

    Zariffard, M Reza; Anastos, Kathryn; French, Audrey L; Munyazesa, Elisaphane; Cohen, Mardge; Landay, Alan L; Spear, Gregory T

    2015-01-01

    Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration. Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA. IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs. These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract.

  16. A Subset of Membrane-Altering Agents and γ-Secretase Modulators Provoke Nonsubstrate Cleavage by Rhomboid Proteases

    Directory of Open Access Journals (Sweden)

    Siniša Urban

    2014-09-01

    Full Text Available Rhomboid proteases are integral membrane enzymes that regulate cell signaling, adhesion, and organelle homeostasis pathways, making substrate specificity a key feature of their function. Interestingly, we found that perturbing the membrane pharmacologically in living cells had little effect on substrate processing but induced inappropriate cleavage of nonsubstrates by rhomboid proteases. A subclass of drugs known to modulate γ-secretase activity acted on the membrane directly and induced nonsubstrate cleavage by rhomboid proteases but left true substrate cleavage sites unaltered. These observations highlight an active role for the membrane in guiding rhomboid selectivity and caution that membrane-targeted drugs should be evaluated for cross-activity against membrane-resident enzymes that are otherwise unrelated to the intended drug target. Furthermore, some γ-secretase-modulating activity or toxicity could partly result from global membrane effects.

  17. Wide-Field Gamma-Spectrometer BDRG: GRB Monitor On-Board the Lomonosov Mission

    Science.gov (United States)

    Svertilov, S. I.; Panasyuk, M. I.; Bogomolov, V. V.; Amelushkin, A. M.; Barinova, V. O.; Galkin, V. I.; Iyudin, A. F.; Kuznetsova, E. A.; Prokhorov, A. V.; Petrov, V. L.; Rozhkov, G. V.; Yashin, I. V.; Gorbovskoy, E. S.; Lipunov, V. M.; Park, I. H.; Jeong, S.; Kim, M. B.

    2018-02-01

    The study of GRB prompt emissions (PE) is one of the main goals of the Lomonosov space mission. The payloads of the GRB monitor (BDRG) with the wide-field optical cameras (SHOK) and the ultra-fast flash observatory (UFFO) onboard the Lomonosov satellite are intended for the observation of GRBs, and in particular, their prompt emissions. The BDRG gamma-ray spectrometer is designed to obtain the temporal and spectral information of GRBs in the energy range of 10-3000 keV as well as to provide GRB triggers on several time scales (10 ms, 1 s and 20 s) for ground and space telescopes, including the UFFO and SHOK. The BDRG instrument consists of three identical detector boxes with axes shifted by 90° from each other. This configuration allows us to localize a GRB source in the sky with an accuracy of ˜ 2°. Each BDRG box contains a phoswich NaI(Tl)/CsI(Tl) scintillator detector. A thick CsI(Tl) crystal in size of \\varnothing 130 × 17 mm is placed underneath the NaI(Tl) as an active shield in the soft energy range and as the main detector in the hard energy range. The ratio of the CsI(Tl) to NaI(Tl) event rates at varying energies can be employed as an independent metric to distinguish legitimate GRB signals from false positives originating from electrons in near-Earth vicinities. The data from three detectors are collected in a BA BDRG information unit, which generates a GRB trigger and a set of data frames in output format. The scientific data output is ˜ 500 Mb per day, including ˜ 180 Mb of continuous data for events with durations in excess of 100 ms for 16 channels in each detector, detailed energy spectra, and sets of frames with ˜ 5 Mb of detailed information for each burst-like event. A number of pre-flight tests including those for the trigger algorithm and calibration were carried out to confirm the reliability of the BDRG for operation in space.

  18. GRB 090227B: THE MISSING LINK BETWEEN THE GENUINE SHORT AND LONG GAMMA-RAY BURSTS

    Energy Technology Data Exchange (ETDEWEB)

    Muccino, M.; Ruffini, R.; Bianco, C. L.; Izzo, L.; Penacchioni, A. V. [Dip. di Fisica and ICRA, Sapienza Universita di Roma, Piazzale Aldo Moro 5, I-00185 Rome (Italy)

    2013-02-15

    The time-resolved spectral analysis of GRB 090227B, made possible by the Fermi-GBM data, allows us to identify in this source the missing link between the genuine short and long gamma-ray bursts (GRBs). Within the Fireshell model of the GRBs we predict genuine short GRBs: bursts with the same inner engine of the long bursts but endowed with a severely low value of the baryon load, B {approx}< 5 Multiplication-Sign 10{sup -5}. A first energetically predominant emission occurs at the transparency of the e {sup +} e {sup -} plasma, the Proper-GRB (P-GRB), followed by a softer emission, the extended afterglow. The typical separation between the two emissions is expected to be of the order of 10{sup -3}-10{sup -2} s. We identify the P-GRB of GRB 090227B in the first 96 ms of emission, where a thermal component with the temperature kT = (517 {+-} 28) keV and a flux comparable with the non-thermal part of the spectrum is observed. This non-thermal component as well as the subsequent emission, where there is no evidence for a thermal spectrum, is identified with the extended afterglow. We deduce a theoretical cosmological redshift z = 1.61 {+-} 0.14. We then derive the total energy E{sup tot}{sub e{sup +}e{sup -}}= (2.83{+-}0.15) Multiplication-Sign 10{sup 53} erg, the baryon load B = (4.13 {+-} 0.05) Multiplication-Sign 10{sup -5}, the Lorentz {Gamma} factor at transparency {Gamma}{sub tr} = (1.44 {+-} 0.01) Multiplication-Sign 10{sup 4}, and the intrinsic duration {Delta}t' {approx} 0.35 s. We also determine the average density of the circumburst medium (CBM), (n {sub CBM}) = (1.90 {+-} 0.20) Multiplication-Sign 10{sup -5} particles cm{sup -3}. There is no evidence of beaming in the system. In view of the energetics and of the baryon load of the source, as well as of the low interstellar medium and of the intrinsic timescale of the signal, we identify the GRB progenitor as a binary neutron star. From the recent progress in the theory of neutron stars, we obtain

  19. Implementation of a combinatorial cleavage and deprotection scheme

    DEFF Research Database (Denmark)

    Nielsen, John; Rasmussen, Palle H.

    1996-01-01

    Phthalhydrazide libraries are synthesized in solution from substituted hydrazines and phthalimides in several different library formats including single compounds, indexed sub-libraries and a full library. When carried out during solid-phase synthesis, this combinatorial cleavage and deprotection...

  20. MODELING THE EARLY AFTERGLOW IN THE SHORT AND HARD GRB 090510

    Energy Technology Data Exchange (ETDEWEB)

    Fraija, N.; Lee, W. H. [Instituto de Astronomía, Universidad Nacional Autónoma de México, Apdo. Postal 70-264, Cd. Universitaria, 04510 Ciudad de México, DF (Mexico); Veres, P. [Center for Space Plasma and Aeronomic Research (CSPAR), University of Alabama in Huntsville, Huntsville, AL 35899 (United States); Duran, R. Barniol, E-mail: nifraija@astro.unam.mx, E-mail: wlee@astro.unam.mx, E-mail: pv0004@uah.edu, E-mail: rbarniol@purdue.edu [Department of Physics and Astronomy, Purdue University, 525 Northwestern Avenue, West Lafayette, IN 47907 (United States)

    2016-11-01

    The bright, short, and hard GRB 090510 was detected by all instruments aboard the Fermi and Swift satellites. The multiwavelength observations of this burst presented similar features to the Fermi -LAT-detected gamma-ray bursts. In the framework of the external shock model of early afterglow, a leptonic scenario that evolves in a homogeneous medium is proposed to revisit GRB 090510 and explain the multiwavelength light curve observations presented in this burst. These observations are consistent with the evolution of a jet before and after the jet break. The long-lasting LAT, X-ray, and optical fluxes are explained in the synchrotron emission from the adiabatic forward shock. Synchrotron self-Compton emission from the reverse shock is consistent with the bright LAT peak provided that the progenitor environment is entrained with strong magnetic fields. It could provide compelling evidence of magnetic field amplification in the neutron star merger.

  1. Fermi observations of high-energy gamma-ray emission from GRB 080916C.

    Science.gov (United States)

    Abdo, A A; Ackermann, M; Arimoto, M; Asano, K; Atwood, W B; Axelsson, M; Baldini, L; Ballet, J; Band, D L; Barbiellini, G; Baring, M G; Bastieri, D; Battelino, M; Baughman, B M; Bechtol, K; Bellardi, F; Bellazzini, R; Berenji, B; Bhat, P N; Bissaldi, E; Blandford, R D; Bloom, E D; Bogaert, G; Bogart, J R; Bonamente, E; Bonnell, J; Borgland, A W; Bouvier, A; Bregeon, J; Brez, A; Briggs, M S; Brigida, M; Bruel, P; Burnett, T H; Burrows, D; Busetto, G; Caliandro, G A; Cameron, R A; Caraveo, P A; Casandjian, J M; Ceccanti, M; Cecchi, C; Celotti, A; Charles, E; Chekhtman, A; Cheung, C C; Chiang, J; Ciprini, S; Claus, R; Cohen-Tanugi, J; Cominsky, L R; Connaughton, V; Conrad, J; Costamante, L; Cutini, S; Deklotz, M; Dermer, C D; de Angelis, A; de Palma, F; Digel, S W; Dingus, B L; do Couto E Silva, E; Drell, P S; Dubois, R; Dumora, D; Edmonds, Y; Evans, P A; Fabiani, D; Farnier, C; Favuzzi, C; Finke, J; Fishman, G; Focke, W B; Frailis, M; Fukazawa, Y; Funk, S; Fusco, P; Gargano, F; Gasparrini, D; Gehrels, N; Germani, S; Giebels, B; Giglietto, N; Giommi, P; Giordano, F; Glanzman, T; Godfrey, G; Goldstein, A; Granot, J; Greiner, J; Grenier, I A; Grondin, M-H; Grove, J E; Guillemot, L; Guiriec, S; Haller, G; Hanabata, Y; Harding, A K; Hayashida, M; Hays, E; Hernando Morat, J A; Hoover, A; Hughes, R E; Jóhannesson, G; Johnson, A S; Johnson, R P; Johnson, T J; Johnson, W N; Kamae, T; Katagiri, H; Kataoka, J; Kavelaars, A; Kawai, N; Kelly, H; Kennea, J; Kerr, M; Kippen, R M; Knödlseder, J; Kocevski, D; Kocian, M L; Komin, N; Kouveliotou, C; Kuehn, F; Kuss, M; Lande, J; Landriu, D; Larsson, S; Latronico, L; Lavalley, C; Lee, B; Lee, S-H; Lemoine-Goumard, M; Lichti, G G; Longo, F; Loparco, F; Lott, B; Lovellette, M N; Lubrano, P; Madejski, G M; Makeev, A; Marangelli, B; Mazziotta, M N; McBreen, S; McEnery, J E; McGlynn, S; Meegan, C; Mészáros, P; Meurer, C; Michelson, P F; Minuti, M; Mirizzi, N; Mitthumsiri, W; Mizuno, T; Moiseev, A A; Monte, C; Monzani, M E; Moretti, E; Morselli, A; Moskalenko, I V; Murgia, S; Nakamori, T; Nelson, D; Nolan, P L; Norris, J P; Nuss, E; Ohno, M; Ohsugi, T; Okumura, A; Omodei, N; Orlando, E; Ormes, J F; Ozaki, M; Paciesas, W S; Paneque, D; Panetta, J H; Parent, D; Pelassa, V; Pepe, M; Perri, M; Pesce-Rollins, M; Petrosian, V; Pinchera, M; Piron, F; Porter, T A; Preece, R; Rainò, S; Ramirez-Ruiz, E; Rando, R; Rapposelli, E; Razzano, M; Razzaque, S; Rea, N; Reimer, A; Reimer, O; Reposeur, T; Reyes, L C; Ritz, S; Rochester, L S; Rodriguez, A Y; Roth, M; Ryde, F; Sadrozinski, H F-W; Sanchez, D; Sander, A; Saz Parkinson, P M; Scargle, J D; Schalk, T L; Segal, K N; Sgrò, C; Shimokawabe, T; Siskind, E J; Smith, D A; Smith, P D; Spandre, G; Spinelli, P; Stamatikos, M; Starck, J-L; Stecker, F W; Steinle, H; Stephens, T E; Strickman, M S; Suson, D J; Tagliaferri, G; Tajima, H; Takahashi, H; Takahashi, T; Tanaka, T; Tenze, A; Thayer, J B; Thayer, J G; Thompson, D J; Tibaldo, L; Torres, D F; Tosti, G; Tramacere, A; Turri, M; Tuvi, S; Usher, T L; van der Horst, A J; Vigiani, L; Vilchez, N; Vitale, V; von Kienlin, A; Waite, A P; Williams, D A; Wilson-Hodge, C; Winer, B L; Wood, K S; Wu, X F; Yamazaki, R; Ylinen, T; Ziegler, M

    2009-03-27

    Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.

  2. The bright optical flash and afterglow from the gamma-ray burst GRB 130427A.

    Science.gov (United States)

    Vestrand, W T; Wren, J A; Panaitescu, A; Wozniak, P R; Davis, H; Palmer, D M; Vianello, G; Omodei, N; Xiong, S; Briggs, M S; Elphick, M; Paciesas, W; Rosing, W

    2014-01-03

    The optical light generated simultaneously with x-rays and gamma rays during a gamma-ray burst (GRB) provides clues about the nature of the explosions that occur as massive stars collapse. We report on the bright optical flash and fading afterglow from powerful burst GRB 130427A. The optical and >100-megaelectron volt (MeV) gamma-ray flux show a close correlation during the first 7000 seconds, which is best explained by reverse shock emission cogenerated in the relativistic burst ejecta as it collides with surrounding material. At later times, optical observations show the emergence of emission generated by a forward shock traversing the circumburst environment. The link between optical afterglow and >100-MeV emission suggests that nearby early peaked afterglows will be the best candidates for studying gamma-ray emission at energies ranging from gigaelectron volts to teraelectron volts.

  3. The extraordinarily bright optical afterglow of GRB 991208 and its host galaxy

    DEFF Research Database (Denmark)

    Castro-Tirado, A.J.; Sokolov, V.V.; Gorosabel, J.

    2001-01-01

    that GRB 991208 is at 3.7 Gpc (for H-0 = 60 km s(-1) Mpc(-1), Omega (0) = 1 and Lambda (0) = 0), implying an isotropic energy release of 1.15 10(53) erg which may. be relaxed by beaming by a factor >10(2). Precise astrometry indicates that the GRB coincides within 0.2" with the host galaxy, thus supporting...... a massive star origin. The absolute magnitude of the galaxy is M-B = -18.2, well below the knee of the galaxy luminosity function and we derive a star-forming rate of (11.5 +/- 7.1) M-circle dot yr(-1), which is much larger than the present-day rate in our Galaxy. The quasi simultaneous broad...

  4. Concluding Remarks: The Current Status and Future Prospects for GRB Astronomy

    Science.gov (United States)

    Gehrels, Neil

    2009-01-01

    We are in a remarkable period of discovery in GRB astronomy. The current satellites including Swift, Fermi. AGILE and INTEGRAL are detecting and observing bursts of all varieties. Increasing capabilities for follow-up observations on the ground and in space are leading to rapid and deep coverage across the electromagnetic spectrum, The future will see continued operation of the current experiments and with future missions like SVOM plus possible rni_Ssions like JANUS and EXIST. An exciting expansion of capabilities is occurring in areas of gravitational waves and neutrinos that could open new windows on the GRB phenomenon. Increased IR capabilities on the ground and with missions like JWST will enable further exploration of high redshift bursts. The future is bright.

  5. A magnetically driven origin for the low luminosity GRB 170817A associated with GW170817

    Science.gov (United States)

    Tong, Hao; Yu, Cong; Huang, Lei

    2018-06-01

    The gamma-ray burst GR170817A associated with GW170817 is subluminous and subenergetic compared with other typical short gamma-ray bursts. It may be due to a relativistic jet viewed off-axis, or a structured jet or cocoon emission. Giant flares from magnetars may possibly be ruled out. However, the luminosity and energetics of GRB 170817A are coincident with those of magnetar giant flares. After the coalescence of a binary neutron star, a hypermassive neutron star may be formed. The hypermassive neutron star may have a magnetar-strength magnetic field. During the collapse of this hypermassive neutron star, magnetic field energy will also be released. This giant-flare-like event may explain the luminosity and energetics of GRB 170817A. Bursts with similar luminosity and energetics are expected in future neutron star-neutron star or neutron star-black hole mergers.

  6. Fermi Observations of high-energy gamma-ray emissions from GRB 080916C

    CERN Document Server

    Abdo, A A; Arimoto, M; Asano, K; Atwood, W B; Axelsson, M; Baldini, L; Ballet, J; Band, D L; Barbiellini, Guido; Baring, Matthew G; Bastieri, Denis; Battelino, M; Baughman, B M; Bechtol, K; Bellardi, F; Bellazzini, R; Berenji, B; Bhat, P N; Bissaldi, E; Blandford, R D; Bloom, Elliott D; Bogaert, G; Bogart, J R; Bonamente, E; Bonnell, J; Borgland, A W; Bouvier, A; Bregeon, J; Brez, A; Briggs, M S; Brigida, M; Bruel, P; Burnett, Thompson H; Burrows, David N; Busetto, Giovanni; Caliandro, G A; Cameron, R A; Caraveo, P A; Casandjian, J M; Ceccanti, M; Cecchi, C; Celotti, Annalisa; Charles, E; Chekhtman, A; Cheung, C.C.Teddy; Chiang, J; Ciprini, S; Claus, R; Cohen-Tanugi, Johann; Cominsky, Lynn R; Connaughton, V; Conrad, J; Costamante, L; Cutini, S; DeKlotz, M; Dermer, C D; De Angelis, Alessandro; de Palma, F; Digel, S W; Dingus, B L; do Couto e Silva, Eduardo; Drell, P S; Dubois, R; Dumora, D; Edmonds, Y; Evans, P A; Fabiani, D; Farnier, C; Favuzzi, C; Finke, Justin D; Fishman, G; Focke, W B; Frailis, M; Fukazawa, Y; Funk, S; Fusco, P; Gargano, F; Gasparrini, D; Gehrels, N; Germani, S; Giebels, B; Giglietto, N; Giommi, P; Giordano, F; Glanzman, Thomas Lynn; Godfrey, Gary L; Goldstein, A; Granot, J; Greiner, J; Grenier, I A; Grondin, M H; Grove, J.Eric; Guillemot, L; Guiriec, S; Haller, G; Hanabata, Y; Harding, Alice K; Hayashida, M; Hays, Elizabeth A; Hernando Morata, J A; Hoover, A; Hughes, R E; Johannesson, G; Johnson, A S; Johnson, R P; Johnson, T J; Johnson, W N; Kamae, Tsuneyoshi; Katagiri, H; Kataoka, J; Kavelaars, A; Kawai, N; Kelly, H; Kennea, J; Kerr, M; Kippen, R M; Knodlseder, J; Kocevski, D; Kocian, M L; Komin, N; Kouveliotou, C; Kuehn, Frederick Gabriel Ivar; Kuss, Michael; Lande, J; Landriu, D; Larsson, S; Latronico, L; Lavalley, C; Lee, B; Lee, S H; Lemoine-Goumard, M; Lichti, G G; Longo, F; Loparco, F; Lott, B; Lovellette, M N; Lubrano, Pasquale; Madejski, G M; Makeev, A; Marangelli, B; Mazziotta, M N; McBreen, Sheila; McEnery, J E; McGlynn, S; Meegan, C; Miszaros, P; Meurer, C; Michelson, P F; Minuti, M; Mirizzi, N; Mitthumsiri, W; Mizuno, T; Moiseev, A A; Monte, C; Monzani, M E; Moretti, E; Morselli, A; Moskalenko, Igor Vladimirovich; Murgia, Simona; Nakamori, T; Nelson, D; Nolan, P L; Norris, J P; Nuss, E; Ohno, M; Ohsugi, Takashi; Okumura, Akira; Omodei, N; Orlando, E; Ormes, J F; Ozaki, M; Paciesas, W S; Paneque, D; Panetta, J H; Parent, D; Pelassa, V; Pepe, M; Perri, M; Pesce-Rollins, M; Petrosian, Vahe; Pinchera, M; Piron, F; Porter, Troy A; Preece, R; Rainr, S; Ramirez-Ruiz, E; Rando, R; Rapposelli, E; Razzano, M; Razzaque, Soebur; Rea, N; Reimer, A; Reimer, O; Reposeur, Thierry; Reyes, Luis C; Ritz, S; Rochester, L S; Rodriguez, A Y; Roth, M; Ryde, F; Sadrozinski, H F W; Sanchez, D; Sander, A; Parkinson, P.M.Saz; Scargle, J D; Schalk, T L; Segal, K N; Sgro, C; Shimokawabe, T; Siskind, E J; Smith, D A; Smith, P D; Spandre, G; Spinelli, P; Stamatikos, M; Starck, Jean-Luc; Stecker, Floyd William; Steinle, H; Stephens, T E; Strickman, M S; Suson, Daniel J; Tagliaferri, G.; Tajima, Hiroyasu; Takahashi, H; Takahashi, T; Tanaka, T; Tenze, A; Thayer, J B; Thayer, J G; Thompson, D J; Tibaldo, L; Torres, Diego F; Tosti, G; Tramacere, A; Turri, M; Tuvi, S; Usher, T L; van der Horst, A J; Vigiani, L; Vilchez, N; Vitale, V; von Kienlin, A; Waite, A P; Williams, D A; Wilson-Hodge, C; Winer, B L; Wood, K S; Wu, X F; Yamazaki, R; Ylinen, T; Ziegler, M

    2009-01-01

    Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.

  7. Cleavage events and sperm dynamics in chick intrauterine embryos.

    Directory of Open Access Journals (Sweden)

    Hyung Chul Lee

    Full Text Available This study was undertaken to elucidate detailed event of early embryogenesis in chicken embryos using a noninvasive egg retrieval technique before oviposition. White Leghorn intrauterine eggs were retrieved from 95 cyclic hens aged up to 54-56 weeks and morphogenetic observation was made under both bright field and fluorescent image in a time course manner. Differing from mammals, asymmetric cleavage to yield preblastodermal cells was observed throughout early embryogenesis. The first two divisions occurred synchronously and four polarized preblastodermal cells resulted after cruciform cleavage. Then, asynchronous cleavage continued in a radial manner and overall cell size in the initial cleavage region was smaller than that in the distal area. Numerous sperms were visible, regardless of zygotic nuclei formation. Condensed sperm heads were present mainly in the perivitelline space and cytoplasm, and rarely in the yolk region, while decondensed sperm heads were only visible in the yolk. In conclusion, apparent differences in sperm dynamics and early cleavage events compared with mammalian embryos were detected in chick embryo development, which demonstrated polarized cleavage with penetrating supernumerary sperm into multiple regions.

  8. Dynamics of bleomycin interaction with a strongly bound hairpin DNA substrate, and implications for cleavage of the bound DNA.

    Science.gov (United States)

    Bozeman, Trevor C; Nanjunda, Rupesh; Tang, Chenhong; Liu, Yang; Segerman, Zachary J; Zaleski, Paul A; Wilson, W David; Hecht, Sidney M

    2012-10-31

    Recent studies involving DNAs bound strongly by bleomycins have documented that such DNAs are degraded by the antitumor antibiotic with characteristics different from those observed when studying the cleavage of randomly chosen DNAs in the presence of excess Fe·BLM. In the present study, surface plasmon resonance has been used to characterize the dynamics of BLM B(2) binding to a strongly bound hairpin DNA, to define the effects of Fe(3+), salt, and temperature on BLM-DNA interaction. One strong primary DNA binding site, and at least one much weaker site, were documented. In contrast, more than one strong cleavage site was found, an observation also made for two other hairpin DNAs. Evidence is presented for BLM equilibration between the stronger and weaker binding sites in a way that renders BLM unavailable to other, less strongly bound DNAs. Thus, enhanced binding to a given site does not necessarily result in increased DNA degradation at that site; i.e., for strongly bound DNAs, the facility of DNA cleavage must involve other parameters in addition to the intrinsic rate of C-4' H atom abstraction from DNA sugars.

  9. A Strong Limit on the Very-high-energy Emission from GRB 150323A

    Science.gov (United States)

    Abeysekara, A. U.; Archer, A.; Benbow, W.; Bird, R.; Brose, R.; Buchovecky, M.; Bugaev, V.; Connolly, M. P.; Cui, W.; Errando, M.; Falcone, A.; Feng, Q.; Finley, J. P.; Flinders, A.; Fortson, L.; Furniss, A.; Gillanders, G. H.; Hütten, M.; Hanna, D.; Hervet, O.; Holder, J.; Hughes, G.; Humensky, T. B.; Johnson, C. A.; Kaaret, P.; Kar, P.; Kelley-Hoskins, N.; Kertzman, M.; Kieda, D.; Krause, M.; Krennrich, F.; Lang, M. J.; Lin, T. T. Y.; Maier, G.; McArthur, S.; Moriarty, P.; Mukherjee, R.; O’Brien, S.; Ong, R. A.; Park, N.; Perkins, J. S.; Petrashyk, A.; Pohl, M.; Popkow, A.; Pueschel, E.; Quinn, J.; Ragan, K.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Rulten, C.; Sadeh, I.; Santander, M.; Sembroski, G. H.; Shahinyan, K.; Tyler, J.; Wakely, S. P.; Weiner, O. M.; Weinstein, A.; Wells, R. M.; Wilcox, P.; Wilhelm, A.; Williams, D. A.; Zitzer, B.; VERITAS Collaboration; Vurm, Indrek; Beloborodov, Andrei

    2018-04-01

    On 2015 March 23, the Very Energetic Radiation Imaging Telescope Array System (VERITAS) responded to a Swift-Burst Alert Telescope (BAT) detection of a gamma-ray burst, with observations beginning 270 s after the onset of BAT emission, and only 135 s after the main BAT emission peak. No statistically significant signal is detected above 140 GeV. The VERITAS upper limit on the fluence in a 40-minute integration corresponds to about 1% of the prompt fluence. Our limit is particularly significant because the very-high-energy (VHE) observation started only ∼2 minutes after the prompt emission peaked, and Fermi-Large Area Telescope observations of numerous other bursts have revealed that the high-energy emission is typically delayed relative to the prompt radiation and lasts significantly longer. Also, the proximity of GRB 150323A (z = 0.593) limits the attenuation by the extragalactic background light to ∼50% at 100–200 GeV. We conclude that GRB 150323A had an intrinsically very weak high-energy afterglow, or that the GeV spectrum had a turnover below ∼100 GeV. If the GRB exploded into the stellar wind of a massive progenitor, the VHE non-detection constrains the wind density parameter to be A ≳ 3 × 1011 g cm‑1, consistent with a standard Wolf–Rayet progenitor. Alternatively, the VHE emission from the blast wave would be weak in a very tenuous medium such as the interstellar medium, which therefore cannot be ruled out as the environment of GRB 150323A.

  10. ASTROSAT CZT IMAGER OBSERVATIONS OF GRB 151006A: TIMING, SPECTROSCOPY, AND POLARIZATION STUDY

    Energy Technology Data Exchange (ETDEWEB)

    Rao, A. R.; Chand, Vikas; Hingar, M. K.; Iyyani, S.; Khanna, Rakesh; Kutty, A. P. K.; Malkar, J. P.; Paul, D. [Department of Astronomy and Astrophysics, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai (India); Bhalerao, V. B.; Bhattacharya, D.; Dewangan, G. C.; Pawar, Pramod; Vibhute, A. M. [Inter University Center for Astronomy and Astrophysics, Pune (India); Chattopadhyay, T.; Mithun, N. P. S.; Vadawale, S. V.; Vagshette, N. [Physical Research Laboratory, Ahmedabad (India); Basak, R. [Nicolaus Copernicus Astronomical Center, Polish Academy of Sciences, Warsaw (Poland); Pradeep, P.; Samuel, Essy, E-mail: arrao@tifr.res.in [Vikram Sarabhai Space Centre, Thiruvananthapuram (India); and others

    2016-12-10

    AstroSat is a multi-wavelength satellite launched on 2015 September 28. The CZT Imager of AstroSat on its very first day of operation detected a long duration gamma-ray burst (GRB), namely GRB 151006A. Using the off-axis imaging and spectral response of the instrument, we demonstrate that the CZT Imager can localize this GRB correctly to about a few degrees, and it can provide, in conjunction with Swift , spectral parameters similar to those obtained from Fermi /GBM. Hence, the CZT Imager would be a useful addition to the currently operating GRB instruments ( Swift and Fermi ). Specifically, we argue that the CZT Imager will be most useful for the short hard GRBs by providing localization for those detected by Fermi and spectral information for those detected only by Swift . We also provide preliminary results on a new exciting capability of this instrument: the CZT Imager is able to identify Compton scattered events thereby providing polarization information for bright GRBs. GRB 151006A, in spite of being relatively faint, shows hints of a polarization signal at 100–300 keV (though at a low significance level). We point out that the CZT Imager should provide significant time resolved polarization measurements for GRBs that have fluence three times higher than that of GRB 151006A. We estimate that the number of such bright GRBs detectable by the CZT Imager is five to six per year. The CZT Imager can also act as a good hard X-ray monitoring device for possible electromagnetic counterparts of gravitational wave events.

  11. A MATURE DUSTY STAR-FORMING GALAXY HOSTING GRB 080607 AT z = 3.036

    International Nuclear Information System (INIS)

    Chen, Hsiao-Wen; Perley, Daniel A.; Cenko, S. Bradley; Bloom, Joshua S.; Wilson, Christine D.; Levan, Andrew J.; Prochaska, Jason X.; Tanvir, Nial R.; Dessauges-Zavadsky, Miroslava; Pettini, Max

    2010-01-01

    We report the discovery of the host galaxy of Swift dark burst GRB 080607 at z GRB = 3.036. GRB 080607 is a unique case of a highly extinguished (A V ∼ 3 mag) afterglow that was yet sufficiently bright for high-quality absorption-line spectroscopy. The host galaxy is clearly resolved in deep Hubble Space Telescope (HST) WF3/IR F160W images and well detected in the Spitzer IRAC 3.5 μm and 4.5 μm channels, while displaying little/no fluxes in deep optical images from Keck and Magellan. The extremely red optical-infrared colors are consistent with the large extinction seen in the afterglow light, suggesting that the large amount of dust and gas surface mass density seen along the afterglow sight line is not merely local but likely reflects the global dust content across the entire host galaxy. Adopting the dust properties and metallicity of the host interstellar medium derived from studies of early-time afterglow light and absorption-line spectroscopy, we perform a stellar population synthesis analysis of the observed spectral energy distribution to constrain the intrinsic luminosity and stellar population of this dark burst host. The host galaxy is best described by an exponentially declining star formation rate of e-folding time τ = 2 Gyr and an age of ∼2 Gyr. We also derive an extinction-corrected star formation rate of SFR ∼ 125 h -2 M sun yr -1 and a total stellar mass of M * ∼ 4 x 10 11 h -2 M sun . Our study provides an example of massive, dusty star-forming galaxies contributing to the γ-ray burst (GRB) host galaxy population, supporting the notion that long-duration GRBs trace the bulk of cosmic star formation.

  12. Surprise in simplicity: an unusual spectral evolution of a single pulse GRB 151006A

    Science.gov (United States)

    Basak, R.; Iyyani, S.; Chand, V.; Chattopadhyay, T.; Bhattacharya, D.; Rao, A. R.; Vadawale, S. V.

    2017-11-01

    We present a detailed analysis of GRB 151006A, the first gamma-ray burst (GRB) detected by AstroSat Cadmium-Zinc-Telluride Imager (CZTI). We study the long-term spectral evolution by exploiting the capabilities of Fermi and Swift satellites at different phases, which is complemented by the polarization measurement with the CZTI. While the light curve of the GRB in different energy bands shows a simple pulse profile, the spectrum shows an unusual evolution. The first phase exhibits a hard-to-soft evolution until ∼16-20 s, followed by a sudden increase in the spectral peak reaching a few MeV. Such a dramatic change in the spectral evolution in the case of a single pulse burst is reported for the first time. This is captured by all models we used namely, Band function, blackbody+Band and two blackbodies+power law. Interestingly, the Fermi Large Area Telescope also detects its first photon (>100 MeV) during this time. This new injection of energy may be associated with either the beginning of afterglow phase, or a second hard pulse of the prompt emission itself that, however, is not seen in the otherwise smooth pulse profile. By constructing Bayesian blocks and studying the hardness evolution we find a good evidence for a second hard pulse. The Swift data at late epochs (>T90 of the GRB) also show a significant spectral evolution consistent with the early second phase. The CZTI data (100-350 keV), though having low significance (1σ), show high values of polarization in the two epochs (77-94 per cent), in agreement with our interpretation.

  13. Four Years of Real-Time GRB Followup by BOOTES-1B (2005-2008)

    Czech Academy of Sciences Publication Activity Database

    Jelínek, M.; Castro-Tirado, A.J.; de Ugarte Postigo, A.; Kubánek, P.; Guziy, S.; Gorosabel, J.; Cunniffe, R.; Vítek, S.; Hudec, René; Reglero, V.; Sabau-Graziati, L.

    2010-01-01

    Roč. 2010, č. 1 (2010), 432172/1-432172/10 ISSN 1687-7969 R&D Projects: GA ČR GA205/08/1207 Grant - others:GA ČR(CZ) GA102/09/0997; ESA(XE) PECS project No. 98023 Institutional research plan: CEZ:AV0Z10030501 Keywords : observing * GRB * Spain Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics OBOR OECD: Astronomy (including astrophysics,space science)

  14. Prompt gamma-ray emission of GRB 170817A associated to GW 170817: A consistent picture

    Science.gov (United States)

    Ziaeepour, Houri

    2018-05-01

    The short GRB 170817A associated to the first detection of gravitation waves from a Binary Neutron Star (BNS) merger was in many ways unusual. Possible explanations are emission from a cocoon or cocoon break out, off-axis view of a structured or uniform jet, and on-axis ultra-relativistic jet with reduced density and Lorentz factor. Here we use a phenomenological model of shock evolution and synchrotron/self-Compton emission to simulate the prompt emission of GRB 170817A and to test above proposals. We find that synchrotron emission from a mildly relativistic cocoon with a Lorentz factor of 2-3, as considered in the literature, generates a too soft, too long, and too bright prompt emission. Off-axis view of an structured jet with a Lorentz factor of about 10 can reproduce observations, but needs a very efficient transfer of kinetic energy to electrons in internal shocks, which is disfavored by particle in cell simulations. We also comment on cocoon breakout as a mechanism for generation of the prompt gamma-ray. A relativistic jet with a Lorentz factor of about 100 and a density lower than typical short GRBs seems to be the most plausible model and we conclude that GRB 170817A was intrinsically faint. Based on this result and findings of relativistic magnetohydrodynamics simulations of BNS merger in the literature we discuss physical and astronomical conditions, which may lead to such faint short GRBs. We identify small mass difference of progenitor neutron stars, their old age and reduced magnetic field, and anti-alignment of spin-orbit angular momentum induced by environmental gravitational disturbances during the lifetime of the BNS as causes for the faintness of GRB 170817A. We predict that BNS mergers at lower redshifts generate on average fainter GRBs.

  15. Modified gravity (MOG), the speed of gravitational radiation and the event GW170817/GRB170817A

    Science.gov (United States)

    Green, M. A.; Moffat, J. W.; Toth, V. T.

    2018-05-01

    Modified gravity (MOG) is a covariant, relativistic, alternative gravitational theory whose field equations are derived from an action that supplements the spacetime metric tensor with vector and scalar fields. Both gravitational (spin 2) and electromagnetic waves travel on null geodesics of the theory's one metric. MOG satisfies the weak equivalence principle and is consistent with observations of the neutron star merger and gamma ray burster event GW170817/GRB170817A.

  16. GRB 090727 AND GAMMA-RAY BURSTS WITH EARLY-TIME OPTICAL EMISSION

    International Nuclear Information System (INIS)

    Kopač, D.; Gomboc, A.; Japelj, J.; Kobayashi, S.; Mundell, C. G.; Bersier, D.; Cano, Z.; Smith, R. J.; Steele, I. A.; Virgili, F. J.; Guidorzi, C.; Melandri, A.

    2013-01-01

    We present a multi-wavelength analysis of Swift gamma-ray burst GRB 090727, for which optical emission was detected during the prompt gamma-ray emission by the 2 m autonomous robotic Liverpool Telescope and subsequently monitored for a further two days with the Liverpool and Faulkes Telescopes. Within the context of the standard fireball model, we rule out a reverse shock origin for the early-time optical emission in GRB 090727 and instead conclude that the early-time optical flash likely corresponds to emission from an internal dissipation process. Putting GRB 090727 into a broader observational and theoretical context, we build a sample of 36 gamma-ray bursts (GRBs) with contemporaneous early-time optical and gamma-ray detections. From these GRBs, we extract a sub-sample of 18 GRBs, which show optical peaks during prompt gamma-ray emission, and perform detailed temporal and spectral analysis in gamma-ray, X-ray, and optical bands. We find that in most cases early-time optical emission shows sharp and steep behavior, and notice a rich diversity of spectral properties. Using a simple internal shock dissipation model, we show that the emission during prompt GRB phase can occur at very different frequencies via synchrotron radiation. Based on the results obtained from observations and simulation, we conclude that the standard external shock interpretation for early-time optical emission is disfavored in most cases due to sharp peaks (Δt/t < 1) and steep rise/decay indices, and that internal dissipation can explain the properties of GRBs with optical peaks during gamma-ray emission

  17. The ultra-long GRB 111209A. II. Prompt to afterglow and afterglow properties

    Energy Technology Data Exchange (ETDEWEB)

    Stratta, G. [Osservatorio Astronomico di Roma (OAR/INAF), via Frascati 33, I-00040 Monte Porzio Catone (Italy); Gendre, B.; Boër, M. [ARTEMIS, UMR 7250 (CNRS/OCA/UNS), boulevard de l' Observatoire, BP 4229, F-06304 Nice Cedex (France); Atteia, J. L. [Université de Toulouse, UPS-OMP, IRAP, F-31400 Toulouse (France); Coward, D. M.; Howell, E. [School of Physics, University of Western Australia (UWA), Crawley, WA 6009 (Australia); De Pasquale, M.; Oates, S. [Mullard Space Science Laboratory (MSSL), University College London, Holmbury St. Mary, Dorking, Surrey RH5 6NT (United Kingdom); Klotz, A. [IRAP, 14, avenue Edouard Belin, F-31400 Toulouse (France); Piro, L. [Istituto di Astrofisica e Planetologia Spaziali di Roma (IAPS/INAF), via fosso del cavaliere 100, I-00133 Roma (Italy)

    2013-12-10

    The 'ultra-long' gamma-ray burst GRB 111209A at redshift z = 0.677 is the longest GRB ever observed thus far, with a rest frame prompt emission duration of ∼4 hr. In order to explain the burst exceptional longevity, a low-metallicity blue supergiant progenitor was invoked. In this article we further constrain the phenomenology and progenitor properties of this peculiar GRB by performing a multiband temporal and spectral analysis of both the prompt and the afterglow emission. We use proprietary and publicly available data from Swift, Konus WIND, XMM-Newton, and TAROT, as well as from other ground-based optical and radio telescopes. We find some peculiar properties that are possibly connected to the exceptional nature of this burst, namely: (1) an unprecedented large optical delay of 410 ± 50 s between the peak time in gamma-rays and the peak time in the optical of a marked multiwavelength flare; (2) multiwavelength prompt emission spectral modeling requires a certain amount of dust in the circumburst environment. The dust produces a rest frame visual extinction of A{sub V} = 0.3-1.5 mag, and may undergo destruction at late times; and (3) we detect the presence of a hard spectral extra power-law component at the end of the X-ray steep steep decay phase and before the start of the X-ray afterglow, which has never been revealed thus far in past GRBs. The optical afterglow shows more usual properties; it has a flux power-law decay with an index of 1.6 ± 0.1 and a late rebrightening feature observed at ∼1.1 the day after the first Burst Alert Telescope trigger. We discuss our findings in the context of several possible interpretations that have been given thus far of the complex multiband GRB phenomenology and propose a binary channel formation for the blue supergiant progenitor.

  18. The ultra-long GRB 111209A. II. Prompt to afterglow and afterglow properties

    International Nuclear Information System (INIS)

    Stratta, G.; Gendre, B.; Boër, M.; Atteia, J. L.; Coward, D. M.; Howell, E.; De Pasquale, M.; Oates, S.; Klotz, A.; Piro, L.

    2013-01-01

    The 'ultra-long' gamma-ray burst GRB 111209A at redshift z = 0.677 is the longest GRB ever observed thus far, with a rest frame prompt emission duration of ∼4 hr. In order to explain the burst exceptional longevity, a low-metallicity blue supergiant progenitor was invoked. In this article we further constrain the phenomenology and progenitor properties of this peculiar GRB by performing a multiband temporal and spectral analysis of both the prompt and the afterglow emission. We use proprietary and publicly available data from Swift, Konus WIND, XMM-Newton, and TAROT, as well as from other ground-based optical and radio telescopes. We find some peculiar properties that are possibly connected to the exceptional nature of this burst, namely: (1) an unprecedented large optical delay of 410 ± 50 s between the peak time in gamma-rays and the peak time in the optical of a marked multiwavelength flare; (2) multiwavelength prompt emission spectral modeling requires a certain amount of dust in the circumburst environment. The dust produces a rest frame visual extinction of A V = 0.3-1.5 mag, and may undergo destruction at late times; and (3) we detect the presence of a hard spectral extra power-law component at the end of the X-ray steep steep decay phase and before the start of the X-ray afterglow, which has never been revealed thus far in past GRBs. The optical afterglow shows more usual properties; it has a flux power-law decay with an index of 1.6 ± 0.1 and a late rebrightening feature observed at ∼1.1 the day after the first Burst Alert Telescope trigger. We discuss our findings in the context of several possible interpretations that have been given thus far of the complex multiband GRB phenomenology and propose a binary channel formation for the blue supergiant progenitor.

  19. The Ultra-long GRB 111209A. II. Prompt to Afterglow and Afterglow Properties

    Science.gov (United States)

    Stratta, G.; Gendre, B.; Atteia, J. L.; Boër, M.; Coward, D. M.; De Pasquale, M.; Howell, E.; Klotz, A.; Oates, S.; Piro, L.

    2013-12-01

    The "ultra-long" gamma-ray burst GRB 111209A at redshift z = 0.677 is the longest GRB ever observed thus far, with a rest frame prompt emission duration of ~4 hr. In order to explain the burst exceptional longevity, a low-metallicity blue supergiant progenitor was invoked. In this article we further constrain the phenomenology and progenitor properties of this peculiar GRB by performing a multiband temporal and spectral analysis of both the prompt and the afterglow emission. We use proprietary and publicly available data from Swift, Konus WIND, XMM-Newton, and TAROT, as well as from other ground-based optical and radio telescopes. We find some peculiar properties that are possibly connected to the exceptional nature of this burst, namely: (1) an unprecedented large optical delay of 410 ± 50 s between the peak time in gamma-rays and the peak time in the optical of a marked multiwavelength flare; (2) multiwavelength prompt emission spectral modeling requires a certain amount of dust in the circumburst environment. The dust produces a rest frame visual extinction of AV = 0.3-1.5 mag, and may undergo destruction at late times; and (3) we detect the presence of a hard spectral extra power-law component at the end of the X-ray steep steep decay phase and before the start of the X-ray afterglow, which has never been revealed thus far in past GRBs. The optical afterglow shows more usual properties; it has a flux power-law decay with an index of 1.6 ± 0.1 and a late rebrightening feature observed at ~1.1 the day after the first Burst Alert Telescope trigger. We discuss our findings in the context of several possible interpretations that have been given thus far of the complex multiband GRB phenomenology and propose a binary channel formation for the blue supergiant progenitor.

  20. CONSTRAINTS ON THE EMISSION MODEL OF THE 'NAKED-EYE BURST' GRB 080319B

    International Nuclear Information System (INIS)

    Abdo, A. A.; Abeysekara, A. U.; Linnemann, J. T.; Allen, B. T.; Chen, C.; Aune, T.; Berley, D.; Goodman, J. A.; Christopher, G. E.; Kolterman, B. E.; Mincer, A. I.; DeYoung, T.; Dingus, B. L.; Hoffman, C. M.; Ellsworth, R. W.; Gonzalez, M. M.; Granot, J.; Hays, E.; McEnery, J. E.; Hüntemeyer, P. H.

    2012-01-01

    On 2008 March 19, one of the brightest gamma-ray bursts (GRBs) ever recorded was detected by several ground- and space-based instruments spanning the electromagnetic spectrum from radio to gamma rays. With a peak visual magnitude of 5.3, GRB 080319B was dubbed the 'naked-eye' GRB, as an observer under dark skies could have seen the burst without the aid of an instrument. Presented here are results from observations of the prompt phase of GRB 080319B taken with the Milagro TeV observatory. The burst was observed at an elevation angle of 47°. Analysis of the data is performed using both the standard air shower method and the scaler or single-particle technique, which results in a sensitive energy range that extends from ∼5 GeV to >20 TeV. These observations provide the only direct constraints on the properties of the high-energy gamma-ray emission from GRB 080319B at these energies. No evidence for emission is found in the Milagro data, and upper limits on the gamma-ray flux above 10 GeV are derived. The limits on emission between ∼25 and 200 GeV are incompatible with the synchrotron self-Compton model of gamma-ray production and disfavor a corresponding range (2 eV-16 eV) of assumed synchrotron peak energies. This indicates that the optical photons and soft (∼650 keV) gamma rays may not be produced by the same electron population.

  1. Preparation of crystals for characterizing the Grb7 SH2 domain before and after complex formation with a bicyclic peptide antagonist.

    Science.gov (United States)

    Ambaye, Nigus D; Gunzburg, Menachem J; Traore, Daouda A K; Del Borgo, Mark P; Perlmutter, Patrick; Wilce, Matthew C J; Wilce, Jacqueline A

    2014-02-01

    Human growth factor receptor-bound protein 7 (Grb7) is an adapter protein involved in cell growth, migration and proliferation. It is now recognized that Grb7 is an emerging therapeutic target in specific cancer subtypes. Recently, the discovery of a bicyclic peptide inhibitor that targets the Grb7 SH2 domain, named G7-B1, was reported. In an attempt to probe the foundation of its interaction with Grb7, the crystallization and preliminary data collection of both the apo and G7-B1-bound forms of the Grb7 SH2 domain are reported here. Diffraction-quality crystals were obtained using the hanging-drop vapour-diffusion method. After several rounds of microseeding, crystals of the apo Grb7 SH2 domain were obtained that diffracted to 1.8 Å resolution, while those of the G7-B1-Grb7 SH2 domain complex diffracted to 2.2 Å resolution. The apo Grb7 SH2 domain crystallized in the trigonal space group P63, whereas the G7-B1-Grb7 SH2 domain complex crystallized in the monoclinic space group P21. The experimental aspects of crystallization, crystal optimization and data collection and the preliminary data are reported.

  2. GRB 120422A: a Low-Luminosity Gamma-Ray Burst Driven by a Central Engine

    Science.gov (United States)

    Zhang, Bin-Bin; Fan, Yi-Zhong; Shen, Rong-Feng; Xu, Dong; Zhang, Fu-Wen; Wei, Da-Ming; Burrows, David N.; Zhang, Bing; Gehrels, Neil

    2012-01-01

    GRB 120422A is a low-luminosity gamma-ray burst (GRB) associated with a bright supernova, which distinguishesitself by its relatively short T(sub 90) (approximately 5 s) and an energetic and steep-decaying X-ray tail. We analyze the Swift BurstAlert Telescope and X-ray Telescope data and discuss the physical implications. We show that the steep declineearly in the X-ray light curve can be interpreted as the curvature tail of a late emission episode around 58-86 s,with a curved instantaneous spectrum at the end of the emission episode. Together with the main activity in thefirst 20 s and the weak emission from 40 s to 60 s, the prompt emission is variable, which points to a centralengine origin in contrast to a shock-breakout origin, which is used to interpret some other nearby low-luminosity supernova GRBs. Both the curvature effect model and interpreting the early shallow decay as the coasting externalforward shock emission in a wind medium provide a constraint on the bulk Lorentz factor to be around several.Comparing the properties ofGRB 120422A and other supernova GRBs,we find that themain criterion to distinguish engine-driven GRBs from shock-breakout GRBs is the time-averaged -ray luminosity. Engine-driven GRBs likelyhave a luminosity above approximately 10(sup 48) erg s(sup -1).

  3. GRB 110205A: ANATOMY OF A LONG GAMMA-RAY BURST

    International Nuclear Information System (INIS)

    Gendre, B.; Stratta, G.; Atteia, J. L.; Klotz, A.; Boër, M.; Colas, F.; Vachier, F.; Kugel, F.; Rinner, C.; Laas-Bourez, M.; Strajnic, J.

    2012-01-01

    The Swift burst GRB 110205A was a very bright burst visible in the Northern Hemisphere. GRB 110205A was intrinsically long and very energetic and it occurred in a low-density interstellar medium environment, leading to delayed afterglow emission and a clear temporal separation of the main emitting components: prompt emission, reverse shock, and forward shock. Our observations show several remarkable features of GRB 110205A: the detection of prompt optical emission strongly correlated with the Burst Alert Telescope light curve, with no temporal lag between the two; the absence of correlation of the X-ray emission compared to the optical and high-energy gamma-ray ones during the prompt phase; and a large optical re-brightening after the end of the prompt phase, that we interpret as a signature of the reverse shock. Beyond the pedagogical value offered by the excellent multi-wavelength coverage of a gamma-ray burst with temporally separated radiating components, we discuss several questions raised by our observations: the nature of the prompt optical emission and the spectral evolution of the prompt emission at high energies (from 0.5 keV to 150 keV); the origin of an X-ray flare at the beginning of the forward shock; and the modeling of the afterglow, including the reverse shock, in the framework of the classical fireball model.

  4. Evolution of the polarization of the optical afterglow of the gamma-ray burst GRB030329.

    Science.gov (United States)

    Greiner, Jochen; Klose, Sylvio; Reinsch, Klaus; Schmid, Hans Martin; Sari, Re'em; Hartmann, Dieter H; Kouveliotou, Chryssa; Rau, Arne; Palazzi, Eliana; Straubmeier, Christian; Stecklum, Bringfried; Zharikov, Sergej; Tovmassian, Gaghik; Bärnbantner, Otto; Ries, Christoph; Jehin, Emmanuel; Henden, Arne; Kaas, Anlaug A; Grav, Tommy; Hjorth, Jens; Pedersen, Holger; Wijers, Ralph A M J; Kaufer, Andreas; Park, Hye-Sook; Williams, Grant; Reimer, Olaf

    2003-11-13

    The association of a supernova with GRB030329 strongly supports the 'collapsar' model of gamma-ray bursts, where a relativistic jet forms after the progenitor star collapses. Such jets cannot be spatially resolved because gamma-ray bursts lie at cosmological distances; their existence is instead inferred from 'breaks' in the light curves of the afterglows, and from the theoretical desire to reduce the estimated total energy of the burst by proposing that most of it comes out in narrow beams. Temporal evolution of the polarization of the afterglows may provide independent evidence for the jet structure of the relativistic outflow. Small-level polarization ( approximately 1-3 per cent) has been reported for a few bursts, but its temporal evolution has yet to be established. Here we report polarimetric observations of the afterglow of GRB030329. We establish the polarization light curve, detect sustained polarization at the per cent level, and find significant variability. The data imply that the afterglow magnetic field has a small coherence length and is mostly random, probably generated by turbulence, in contrast with the picture arising from the high polarization detected in the prompt gamma-rays from GRB021206 (ref. 18).

  5. A new gamma-ray burst classification scheme from GRB 060614.

    Science.gov (United States)

    Gehrels, N; Norris, J P; Barthelmy, S D; Granot, J; Kaneko, Y; Kouveliotou, C; Markwardt, C B; Mészáros, P; Nakar, E; Nousek, J A; O'Brien, P T; Page, M; Palmer, D M; Parsons, A M; Roming, P W A; Sakamoto, T; Sarazin, C L; Schady, P; Stamatikos, M; Woosley, S E

    2006-12-21

    Gamma-ray bursts (GRBs) are known to come in two duration classes, separated at approximately 2 s. Long-duration bursts originate from star-forming regions in galaxies, have accompanying supernovae when these are near enough to observe and are probably caused by massive-star collapsars. Recent observations show that short-duration bursts originate in regions within their host galaxies that have lower star-formation rates, consistent with binary neutron star or neutron star-black hole mergers. Moreover, although their hosts are predominantly nearby galaxies, no supernovae have been so far associated with short-duration GRBs. Here we report that the bright, nearby GRB 060614 does not fit into either class. Its approximately 102-s duration groups it with long-duration GRBs, while its temporal lag and peak luminosity fall entirely within the short-duration GRB subclass. Moreover, very deep optical observations exclude an accompanying supernova, similar to short-duration GRBs. This combination of a long-duration event without an accompanying supernova poses a challenge to both the collapsar and the merging-neutron-star interpretations and opens the door to a new GRB classification scheme that straddles both long- and short-duration bursts.

  6. Extremely Bright GRB 160625B with Multiple Emission Episodes: Evidence for Long-term Ejecta Evolution

    Energy Technology Data Exchange (ETDEWEB)

    Lü, Hou-Jun; Lü, Jing; Zhong, Shu-Qing; Huang, Xiao-Li; Zhang, Hai-Ming; Lan, Lin; Lu, Rui-Jing; Liang, En-Wei [Guangxi Key Laboratory for Relativistic Astrophysics, Department of Physics, Guangxi University, Nanning 530004 (China); Xie, Wei, E-mail: lhj@gxu.edu.edu, E-mail: lew@gxu.edu.cn [School of Physics, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2017-11-01

    GRB 160625B is an extremely bright GRB with three distinct emission episodes. By analyzing its data observed with the Gamma-Ray Burst Monitor (GBM) and Large Area Telescope (LAT) on board the Fermi mission, we find that a multicolor blackbody (mBB) model can be used to fit very well the spectra of the initial short episode (Episode I) within the hypothesis of photosphere emission of a fireball model. The time-resolved spectra of its main episode (Episode II), which was detected with both GBM and LAT after a long quiescent stage (∼180 s) following the initial episode, can be fitted with a model comprising an mBB component plus a cutoff power-law (CPL) component. This GRB was detected again in the GBM and LAT bands with a long extended emission (Episode III) after a quiescent period of ∼300 s. The spectrum of Episode III is adequately fitted with CPL plus single power-law models, and no mBB component is required. These features may imply that the emission of the three episodes are dominated by distinct physics processes, i.e., Episode I is possible from the cocoon emission surrounding the relativistic jet, Episode II may be from photosphere emission and internal shock of the relativistic jet, and Episode III is contributed by internal and external shocks of the relativistic jet. On the other hand, both X-ray and optical afterglows are consistent with the standard external shocks model.

  7. Beam On Target (BOT) Produces Gamma Ray Burst (GRB) Fireballs and Afterglows

    Science.gov (United States)

    Greyber, H. D.

    1997-12-01

    Unlike the myriads of ad hoc models that have been offered to explain GRB, the BOT process is simply the very common process used worldwide in accelerator laboratories to produce gamma rays. The Strong Magnetic Field (SMF) model postulates an extremely intense, highly relativistic current ring formed during the original gravitational collapse of a distant galaxy when the plasma cloud was permeated by a primordial magnetic field. GRB occur when solid matter (asteroid, white dwarf, neutron star, planet) falls rapidly through the Storage Ring beam producing a very strongly collimated electromagnetic shower, and a huge amount of matter from the target, in the form of a giant, hot, expanding plasma cloud, or ``Fireball,'' is blown off. BOT satisfies all the ``severe constraints imposed on the source of this burst --'' concluded by the CGRO team (Sommer et al, Astrophys. J. 422 L63 (1994)) for the huge intense burst GRB930131, whereas neutron star merger models are ``difficult to reconcile.'' BOT expects the lowest energy gamma photons to arrive very slightly later than higher energy photons due to the time for the shower to penetrate the target. The millisecond spikes in bursts are due to the slender filaments of current that make up the Storage Ring beam. Delayed photons can be explained by a broken target ``rock.'' See H. Greyber in the book ``Compton Gamma Ray Observatory,'' AIP Conf. Proc. 280, 569 (1993).

  8. Multicolour modelling of SN 2013dx associated with GRB 130702A★

    Science.gov (United States)

    Volnova, A. A.; Pruzhinskaya, M. V.; Pozanenko, A. S.; Blinnikov, S. I.; Minaev, P. Yu.; Burkhonov, O. A.; Chernenko, A. M.; Ehgamberdiev, Sh. A.; Inasaridze, R.; Jelinek, M.; Khorunzhev, G. A.; Klunko, E. V.; Krugly, Yu. N.; Mazaeva, E. D.; Rumyantsev, V. V.; Volvach, A. E.

    2017-05-01

    We present optical observations of SN 2013dx, related to the Fermi burst GRB 130702A, which occurred at red shift z = 0.145. It is the second-best sampled gamma-ray burst (GRB)/supernova (SN) after SN 1998bw. The observational light curves contain more than 280 data points in the uBgrRiz filters until 88 d after the burst, and the data were collected from our observational collaboration (Maidanak Observatory, Abastumani Observatory, Crimean Astrophysical Observatory, Mondy Observatory, National Observatory of Turkey and Observatorio del Roque de los Muchachos) and from the literature. We model numerically the multicolour light curves using the one-dimensional radiation hydrodynamical code stella, previously widely implemented for modelling typical non-GRB SNe. The best-fitting model has the following parameters: pre-SN star mass M = 25 M⊙; mass of the compact remnant MCR = 6 M⊙; total energy of the outburst Eoburst = 3.5 × 1052 erg; pre-supernova star radius R = 100 R⊙; M_^{56Ni} = 0.2 M_{⊙}, which is totally mixed through the ejecta; MO = 16.6 M⊙; MSi = 1.2 M⊙ and MFe = 1.2 M⊙, and the radiative efficiency of the SN is 0.1 per cent.

  9. Long-term continuous energy injection in the afterglow of GRB 060729

    International Nuclear Information System (INIS)

    Xu Ming; Huang Yongfeng; Lu Tan

    2009-01-01

    A long plateau phase and an amazing level of brightness have been observed in the X-ray afterglow of GRB 060729. This peculiar light curve is likely due to long-term energy injection in external shock. Here, we present a detailed numerical study of the energy injection process of magnetic dipole radiation from a strongly magnetized millisecond pulsar and model the multi-band afterglow observations. It is found that this model can successfully explain the long plateaus in the observed X-ray and optical afterglow light curves. The sharp break following the plateaus could be due to the rapid decline of the emission power of the central pulsar. At an even later time (∼ 5 x 10 6 s), an obvious jet break appears, which implies a relatively large half opening angle of θ ∼ 0.3 for the GRB ejecta. Due to the energy injection, the Lorentz factor of the outflow is still larger than two even at 10 7 s after the GRB trigger, making the X-ray afterglow of this burst detectable by Chandra even 642 d after the burst.

  10. The Signature of the Central Engine in the Weakest Relativistic Explosions: GRB 100316D

    Science.gov (United States)

    Margutti, R.; Soderberg, A. M.; Wieringa, M. H.; Edwards, P. G.; Chevalier, R. A.; Morsony, B. J.; Barniol Duran, R.; Sironi, L.; Zauderer, B. A.; Milisavljevic, D.; Kamble, A.; Pian, E.

    2013-11-01

    We present late-time radio and X-ray observations of the nearby sub-energetic gamma-ray burst (GRB)100316D associated with supernova (SN) 2010bh. Our broad-band analysis constrains the explosion properties of GRB 100316D to be intermediate between highly relativistic, collimated GRBs and the spherical, ordinary hydrogen-stripped SNe. We find that ~1049 erg is coupled to mildly relativistic (Γ = 1.5-2), quasi-spherical ejecta, expanding into a medium previously shaped by the progenitor mass-loss with a rate of \\dot{M}\\, {\\sim }\\, 10^{-5}\\,M_{\\odot }\\,yr^{-1} (for an assumed wind density profile and wind velocity vw = 1000 km s-1). The kinetic energy profile of the ejecta argues for the presence of a central engine and identifies GRB 100316D as one of the weakest central-engine-driven explosions detected to date. Emission from the central engine is responsible for an excess of soft X-ray radiation that dominates over the standard afterglow at late times (t > 10 days). We connect this phenomenology with the birth of the most rapidly rotating magnetars. Alternatively, accretion onto a newly formed black hole might explain the excess of radiation. However, significant departure from the standard fall-back scenario is required.

  11. The signature of the central engine in the weakest relativistic explosions: GRB 100316D

    International Nuclear Information System (INIS)

    Margutti, R.; Soderberg, A. M.; Sironi, L.; Zauderer, B. A.; Milisavljevic, D.; Kamble, A.; Wieringa, M. H.; Edwards, P. G.; Chevalier, R. A.; Morsony, B. J.; Duran, R. Barniol; Pian, E.

    2013-01-01

    We present late-time radio and X-ray observations of the nearby sub-energetic gamma-ray burst (GRB)100316D associated with supernova (SN) 2010bh. Our broad-band analysis constrains the explosion properties of GRB 100316D to be intermediate between highly relativistic, collimated GRBs and the spherical, ordinary hydrogen-stripped SNe. We find that ∼10 49 erg is coupled to mildly relativistic (Γ = 1.5-2), quasi-spherical ejecta, expanding into a medium previously shaped by the progenitor mass-loss with a rate of M-dot ∼ 10 −5 M ⊙ yr −1 (for an assumed wind density profile and wind velocity v w = 1000 km s –1 ). The kinetic energy profile of the ejecta argues for the presence of a central engine and identifies GRB 100316D as one of the weakest central-engine-driven explosions detected to date. Emission from the central engine is responsible for an excess of soft X-ray radiation that dominates over the standard afterglow at late times (t > 10 days). We connect this phenomenology with the birth of the most rapidly rotating magnetars. Alternatively, accretion onto a newly formed black hole might explain the excess of radiation. However, significant departure from the standard fall-back scenario is required.

  12. BOOTES-IR: near IR follow-up GRB observations by a robotic system

    International Nuclear Information System (INIS)

    Castro-Tirado, A.J.; Postrigo, A. de Ugarte; Jelinek, M.

    2005-01-01

    BOOTES-IR is the extension of the BOOTES experiment, which operates in Southern Spain since 1998, to the near IR (NIR). The goal is to follow up the early stage of the gamma ray burst (GRB) afterglow emission in the NIR, alike BOOTES does already at optical wavelengths. The scientific case that drives the BOOTES-IR performance is the study of GRBs with the support of spacecraft like INTEGRAL, SWIFT and GLAST. Given that the afterglow emission in both, the NIR and the optical, in the instances immediately following a GRB, is extremely bright (reached V = 8.9 in one case), it should be possible to detect this prompt emission at NIR wavelengths too. The combined observations by BOOTES-IR and BOOTES-1 and BOOTES-2 will allow for real time identification of trustworthy candidates to have a high redshift (z > 5). It is expected that, few minutes after a GRB, the IR magnitudes be H ∼ 7-10, hence very high quality spectra can be obtained for objects as far as z = 10 by larger instruments

  13. GRB 091024A and the nature of ultra-long gamma-ray bursts

    International Nuclear Information System (INIS)

    Virgili, F. J.; Mundell, C. G.; Harrison, R.; Kobayashi, S.; Steele, I. A.; Mottram, C. J.; Clay, N. R.; Pal'shin, V.; Guidorzi, C.; Margutti, R.; Chornock, R.; Melandri, A.; Henden, A.; Updike, A. C.; Cenko, S. B.; Tanvir, N. R.; Cucchiara, A.; Gomboc, A.; Levan, A.; Cano, Z.

    2013-01-01

    We present a broadband study of gamma-ray burst (GRB) 091024A within the context of other ultra-long-duration GRBs. An unusually long burst detected by Konus-Wind (KW), Swift, and Fermi, GRB 091024A has prompt emission episodes covering ∼1300 s, accompanied by bright and highly structured optical emission captured by various rapid-response facilities, including the 2 m autonomous robotic Faulkes North and Liverpool Telescopes, KAIT, S-LOTIS, and the Sonoita Research Observatory. We also observed the burst with 8 and 10 m class telescopes and determine the redshift to be z = 1.0924 ± 0.0004. We find no correlation between the optical and γ-ray peaks and interpret the optical light curve as being of external origin, caused by the reverse and forward shock of a highly magnetized jet (R B ≈ 100-200). Low-level emission is detected throughout the near-background quiescent period between the first two emission episodes of the KW data, suggesting continued central-engine activity; we discuss the implications of this ongoing emission and its impact on the afterglow evolution and predictions. We summarize the varied sample of historical GRBs with exceptionally long durations in gamma-rays (≳1000 s) and discuss the likelihood of these events being from a separate population; we suggest ultra-long GRBs represent the tail of the duration distribution of the long GRB population.

  14. SKI2 mediates degradation of RISC 5′-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis

    Science.gov (United States)

    Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter

    2015-01-01

    Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20–24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5′, but not 3′-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5′ to the cleavage site, but several examples of 3′-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5′-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5′-cleavage fragments. PMID:26464441

  15. SKI2 mediates degradation of RISC 5'-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis.

    Science.gov (United States)

    Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter

    2015-12-15

    Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20-24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5', but not 3'-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5' to the cleavage site, but several examples of 3'-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5'-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5'-cleavage fragments. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations

    Science.gov (United States)

    Zuo, Zhicheng; Liu, Jin

    2016-11-01

    The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (spCas9) along with a single guide RNA (sgRNA) has emerged as a versatile toolbox for genome editing. Despite recent advances in the mechanism studies on spCas9-sgRNA-mediated double-stranded DNA (dsDNA) recognition and cleavage, it is still unclear how the catalytic Mg2+ ions induce the conformation changes toward the catalytic active state. It also remains controversial whether Cas9 generates blunt-ended or staggered-ended breaks with overhangs in the DNA. To investigate these issues, here we performed the first all-atom molecular dynamics simulations of the spCas9-sgRNA-dsDNA system with and without Mg2+ bound. The simulation results showed that binding of two Mg2+ ions at the RuvC domain active site could lead to structurally and energetically favorable coordination ready for the non-target DNA strand cleavage. Importantly, we demonstrated with our simulations that Cas9-catalyzed DNA cleavage produces 1-bp staggered ends rather than generally assumed blunt ends.

  17. Determinants of the VP1/2A junction cleavage by the 3C protease in foot-and-mouth disease virus infected cells

    DEFF Research Database (Denmark)

    Kristensen, Thea; Normann, Preben; Gullberg, Maria

    2017-01-01

    . Interestingly, in contrast to the serotype O virus results, no second site mutations occurred within the VP1 coding region of serotype A viruses with the blocked VP1/2A cleavage site. However, some of these viruses acquired changes in the 2C protein that is involved in enterovirus morphogenesis. These results...

  18. Relationship Between Quantitative GRB7 RNA Expression and Recurrence after Adjuvant Anthracycline Chemotherapy in Triple Negative Breast Cancer

    Science.gov (United States)

    Sparano, Joseph A.; Goldstein, Lori J.; Childs, Barrett H.; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L.; Bugarini, Roberto; Rowley, Steve; Perez, Edith; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Kenny, Paraic A.; Sledge, George W.; Gray, Robert

    2012-01-01

    Purpose To perform an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental design RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative RT-PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results GRB7 was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn’s adjusted p value=0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR 2.31, p=0.04 using the median as the split). The 5-year recurrence rates were 10.5% (95% confidence intervals [CI] 7.8%, 14.1%) in the low and 20.4% (95% CI 16.5%, 25.0%) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered. PMID:21933890

  19. Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer.

    Science.gov (United States)

    Sparano, Joseph A; Goldstein, Lori J; Childs, Barrett H; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L; Bugarini, Roberto; Rowley, Steve; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Davidson, Nancy E; Kenny, Paraic A; Sledge, George W; Gray, Robert

    2011-11-15

    To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.

  20. Perturbation with intrabodies reveals that calpain cleavage is required for degradation of huntingtin exon 1.

    Directory of Open Access Journals (Sweden)

    Amber L Southwell

    2011-01-01

    Full Text Available Proteolytic processing of mutant huntingtin (mHtt, the protein that causes Huntington's disease (HD, is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD.We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1 clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V(L12.3, turnover of soluble mHDx-1 in living cells is blocked.These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications.

  1. Evidence of Alternative Cystatin C Signal Sequence Cleavage Which Is Influenced by the A25T Polymorphism.

    Directory of Open Access Journals (Sweden)

    Annie Nguyen

    Full Text Available Cystatin C (Cys C is a small, potent, cysteine protease inhibitor. An Ala25Thr (A25T polymorphism in Cys C has been associated with both macular degeneration and late-onset Alzheimer's disease. Previously, studies have suggested that this polymorphism may compromise the secretion of Cys C. Interestingly, we found that untagged A25T, A25T tagged C-terminally with FLAG, or A25T FLAG followed by green fluorescent protein (GFP, were all secreted as efficiently from immortalized human cells as their wild-type (WT counterparts (e.g., 112%, 100%, and 88% of WT levels from HEK-293T cells, respectively. Supporting these observations, WT and A25T Cys C variants also showed similar intracellular steady state levels. Furthermore, A25T Cys C did not activate the unfolded protein response and followed the same canonical endoplasmic reticulum (ER-Golgi trafficking pathway as WT Cys C. WT Cys C has been shown to undergo signal sequence cleavage between residues Gly26 and Ser27. While the A25T polymorphism did not affect Cys C secretion, we hypothesized that it may alter where the Cys C signal sequence is preferentially cleaved. Under normal conditions, WT and A25T Cys C have the same signal sequence cleavage site after Gly26 (referred to as 'site 2' cleavage. However, in particular circumstances when the residues around site 2 are modified (such as by the presence of an N-terminal FLAG tag immediately after Gly26, or by a Gly26Lys (G26K mutation, A25T has a significantly higher likelihood than WT Cys C of alternative signal sequence cleavage after Ala20 ('site 1' or even earlier in the Cys C sequence. Overall, our results indicate that the A25T polymorphism does not cause a significant reduction in Cys C secretion, but instead predisposes the protein to be cleaved at an alternative signal sequence cleavage site if site 2 is hindered. Additional N-terminal amino acids resulting from alternative signal sequence cleavage may, in turn, affect the protease

  2. Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage

    DEFF Research Database (Denmark)

    Stella, Stefano; Alcón, Pablo; Montoya, Guillermo

    2017-01-01

    involved in DNA unwinding to form a CRISPR RNA (crRNA)-DNA hybrid and a displaced DNA strand. The protospacer adjacent motif (PAM) is recognized by the PAM-interacting domain. The loop-lysine helix-loop motif in this domain contains three conserved lysine residues that are inserted in a dentate manner...... and the crRNA-DNA hybrid, avoiding DNA re-annealing. Mutations in key residues reveal a mechanism linking the PAM and DNA nuclease sites. Analysis of the Cpf1 structures proposes a singular working model of RNA-guided DNA cleavage, suggesting new avenues for redesign of Cpf1....

  3. Secondary isotope effects on alpha-cleavage reactions

    International Nuclear Information System (INIS)

    Ingemann, S.; Hammerum, S.

    1980-01-01

    Kinetic deuterium isotope effects on mass spectral reactions have in several instances been utilized to provide structural information and to answer mechanistic questions. Typically, the influence of the deuterium label on the rate of one of a number of competing reactions has been studied. Secondary isotope effects have usually been assumed to be relatively insignificant in comparison with the observed kinetic effects, even though various workers have shown that secondary isotope effects may indeed exert a considerable influence on the rates of competing simple cleavages. Recent studies have provided quantitative data to show that the mere presence of deuterium atoms up to six bonds away may influence the rate of a simple cleavage reaction. In relation to an investigation of rearrangements accompanying simple cleavage reactions, a semi-quantitative measure was needed of the variation of the secondary isotope effect with the number of bonds between the deuterium label and the point of rupture. The influence has therefore been examined of the presence of remote deuterium atoms on a typical simple cleavage reaction, the α-cleavage of aliphatic amines. As a model compound, N-methyldipentylamine was chosen, systematically labelled with deuterium. (author)

  4. First measurement of H I 21 cm emission from a GRB host galaxy indicates a post-merger system

    Science.gov (United States)

    Arabsalmani, Maryam; Roychowdhury, Sambit; Zwaan, Martin A.; Kanekar, Nissim; Michałowski, Michał J.

    2015-11-01

    We report the detection and mapping of atomic hydrogen in H I 21 cm emission from ESO 184-G82, the host galaxy of the gamma-ray burst 980425. This is the first instance where H I in emission has been detected from a galaxy hosting a gamma-ray burst (GRB). ESO 184-G82 is an isolated galaxy and contains a Wolf-Rayet region close to the location of the GRB and the associated supernova, SN 1998bw. This is one of the most luminous H II regions identified in the local Universe, with a very high inferred density of star formation. The H I 21 cm observations reveal a high H I mass for the galaxy, twice as large as the stellar mass. The spatial and velocity distribution of the H I 21 cm emission reveals a disturbed rotating gas disc, which suggests that the galaxy has undergone a recent minor merger that disrupted its rotation. We find that the Wolf-Rayet region and the GRB are both located in the highest H I column density region of the galaxy. We speculate that the merger event has resulted in shock compression of the gas, triggering extreme star formation activity, and resulting in the formation of both the Wolf-Rayet region and the GRB. The high H I column density environment of the GRB is consistent with the high H I column densities seen in absorption in the host galaxies of high-redshift GRBs.

  5. The LAGO (Large Aperture GRB Observatory) in Peru

    Science.gov (United States)

    Tueros-Cuadros, E.; Otiniano, L.; Chirinos, J.; Soncco, C.; Guevara-Day, W.

    2012-07-01

    The Large Aperture GRBs Observatory is a continental-wide observatory devised to detect high energy (around 100 GeV) component of Gamma Ray Bursts (GRBs), by using the single particle technique in arrays of Water Cherenkov Detectors (WCDs) at high mountain sites of Argentina, Bolivia, Colombia, Guatemala, Mexico, Venezuela and Peru. Details of the instalation and operation of the detectors in Marcapomacocha in Peru at 4550 m.a.s.l. are given. The detector calibration method will also be shown.

  6. A new cultural cleavage in post-modern society

    Directory of Open Access Journals (Sweden)

    Jan-Erik Lane

    2007-09-01

    Full Text Available The attitudes towards gender and homosexuality tend to be linked at the micro level (individuals, which explains the political saliency of this newly emerging cleavage. At the macro level (country, the main finding is that the value orientations towards gender and homosexuality are strongly embedded in the basic cultural or civilisation differences among countries. As developing countries modernise and enter post-modernity, they will also experience the gender cleavage, especially when they adhere to an individualistic culture. Cultural cleavages in the post-modern society, whether in rich or developing countries, can only be properly researched by the survey method. It opens up a large area for both micro and macro analyses in the social sciences.

  7. New Insight into the Cleavage Reaction of Nostoc sp. Strain PCC 7120 Carotenoid Cleavage Dioxygenase in Natural and Nonnatural Carotenoids

    Science.gov (United States)

    Heo, Jinsol; Kim, Se Hyeuk

    2013-01-01

    Carotenoid cleavage dioxygenases (CCDs) are enzymes that catalyze the oxidative cleavage of carotenoids at a specific double bond to generate apocarotenoids. In this study, we investigated the activity and substrate preferences of NSC3, a CCD of Nostoc sp. strain PCC 7120, in vivo and in vitro using natural and nonnatural carotenoid structures. NSC3 cleaved β-apo-8′-carotenal at 3 positions, C-13C-14, C-15C-15′, and C-13′C-14′, revealing a unique cleavage pattern. NSC3 cleaves the natural structure of carotenoids 4,4′-diaponeurosporene, 4,4′-diaponeurosporen-4′-al, 4,4′-diaponeurosporen-4′-oic acid, 4,4′-diapotorulene, and 4,4′-diapotorulen-4′-al to generate novel cleavage products (apo-14′-diaponeurosporenal, apo-13′-diaponeurosporenal, apo-10′-diaponeurosporenal, apo-14′-diapotorulenal, and apo-10′-diapotorulenal, respectively). The study of carotenoids with natural or nonnatural structures produced by using synthetic modules could provide information valuable for understanding the cleavage reactions or substrate preferences of other CCDs in vivo and in vitro. PMID:23524669

  8. Identification of Rbd2 as a candidate protease for sterol regulatory element binding protein (SREBP) cleavage in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinsil; Ha, Hye-Jeong [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Kim, Sujin [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113 (Korea, Republic of); Choi, Ah-Reum [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Lee, Sook-Jeong [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Hoe, Kwang-Lae, E-mail: kwanghoe@cnu.ac.kr [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Kim, Dong-Uk, E-mail: kimdongu@kribb.re.kr [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of)

    2015-12-25

    Lipid homeostasis in mammalian cells is regulated by sterol regulatory element-binding protein (SREBP) transcription factors that are activated through sequential cleavage by Golgi Site-1 and Site-2 proteases. Fission yeast SREBP, Sre1, engages a different mechanism involving the Golgi Dsc E3 ligase complex, but it is not clearly understood exactly how Sre1 is proteolytically cleaved and activated. In this study, we screened the Schizosaccharomyces pombe non-essential haploid deletion collection to identify missing components of the Sre1 cleavage machinery. Our screen identified an additional component of the SREBP pathway required for Sre1 proteolysis named rhomboid protein 2 (Rbd2). We show that an rbd2 deletion mutant fails to grow under hypoxic and hypoxia-mimetic conditions due to lack of Sre1 activity and that this growth phenotype is rescued by Sre1N, a cleaved active form of Sre1. We found that the growth inhibition phenotype under low oxygen conditions is specific to the strain with deletion of rbd2, not any other fission yeast rhomboid-encoding genes. Our study also identified conserved residues of Rbd2 that are required for Sre1 proteolytic cleavage. All together, our results suggest that Rbd2 is a functional SREBP protease with conserved residues required for Sre1 cleavage and provide an important piece of the puzzle to understand the mechanisms for Sre1 activation and the regulation of various biological and pathological processes involving SREBPs. - Highlights: • An rbd2-deleted yeast strain shows defects in growth in response to low oxygen levels. • rbd2-deficient cells fail to generate cleaved Sre1 (Sre1N) under hypoxic conditions. • Expression of Sre1N rescues the rbd2 deletion mutant growth phenotype. • Rbd2 contains conserved residues potentially critical for catalytic activity. • Mutation of the conserved Rbd2 catalytic residues leads to defects in Sre1 cleavage.

  9. Detection of GRB 060927 at z = 5.47: Implications for the Use of Gamma-Ray Bursts as Probes of the End of the Dark Ages

    NARCIS (Netherlands)

    Ruiz-Velasco, A.E.; Swan, H.; Troja, E.; Malesani, D.; Fynbo, J.P.U.; Starling, R.L.C.; Xu, D.; Aharonian, F.; Akerlof, C.; Andersen, M.I.; Ashley, M.C.B.; Barthelmy, S.D.; Bersier, D.F.; Cerón, J.M.; Castro-Tirado, A.J.; Gehrels, N.; Gögüs, E.; Gorosabel, J.; Guidorzi, C.; Güver, T.; Hjorth, J.; Horns, D.; Huang, K.Y.; Jakobsson, P.; Jensen, B.L.; Kiziloglu, Ü.; Kouveliotou, C.; Krimm, H.A.; Ledoux, C.; Levan, A.J.; Marsh, T.; McKay, T.; Melandri, A.; Milvang-Jensen, B.; Mundell, C.G.; O'Brien, P.T.; Özel, M.; Phillips, A.; Quimby, R.; Rowell, G.; Rujopakarn, W.; Rykoff, E.S.; Schaefer, B.E.; Sollerman, J.; Tanvir, N.R.; Thöne, C.C.; Urata, Y.; Vestrand, W.T.; Vreeswijk, P.M.; Watson, D.; Wheeler, J.C.; Wijers, R.A.M.J.; Wren, J.; Yost, S.A.; Yuan, F.; Zhai, M.; Zheng, W.K.

    2007-01-01

    We report on follow-up observations of the gamma-ray burst GRB 060927 using the robotic ROTSE-IIIa telescope and a suite of larger aperture ground-based telescopes. An optical afterglow was detected 20 s after the burst, the earliest rest-frame detection of optical emission from any GRB.

  10. The afterglow of the short/intermediate-duration gamma-ray burst GRB 000301C: A jet at z=2.04

    DEFF Research Database (Denmark)

    Jensen, B.L.; Fynbo, J.U.; Gorosabel, J.

    2001-01-01

    We present Ulysses and NEAR data from the detection of the short or intermediate duration (2 s) gamma-ray burst GRB 000301C (2000 March 1.41 UT). The gamma-ray burst (GRB) was localised by the Inter Planetary Network (IPN) and RXTE to an area of similar to 50 arcmin(2). A fading optical counterpa...

  11. Sensitive and fast mutation detection by solid phase chemical cleavage

    DEFF Research Database (Denmark)

    Hansen, Lise Lotte; Justesen, Just; Kruse, Torben A

    1996-01-01

    We have developed a solid phase chemical cleavage method (SpCCM) for screening large DNA fragments for mutations. All reactions can be carried out in microtiterwells from the first amplification of the patient (or test) DNA through the search for mutations. The reaction time is significantly...... reduced compared to the conventional chemical cleavage method (CCM), and even by using a uniformly labelled probe, the exact position and nature of the mutation can be revealed. The SpCCM is suitable for automatization using a workstation to carry out the reactions and a fluorescent detection-based DNA...

  12. Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction

    Science.gov (United States)

    Mir, Aamir; Chen, Ji; Robinson, Kyle; Lendy, Emma; Goodman, Jaclyn; Neau, David; Golden, Barbara L.

    2016-01-01

    The hammerhead ribozyme is a self-cleaving RNA broadly dispersed across all kingdoms of life. Although it was the first of the small, nucleolytic ribozymes discovered, the mechanism by which it catalyzes its reaction remains elusive. The nucleobase of G12 is well positioned to be a general base, but it is unclear if or how this guanine base becomes activated for proton transfer. Metal ions have been implicated in the chemical mechanism, but no interactions between divalent metal ions and the cleavage site have been observed crystallographically. To better understand how this ribozyme functions, we have solved crystal structures of wild-type and G12A mutant ribozymes. We observe a pH-dependent conformational change centered around G12, consistent with this nucleotide becoming deprotonated. Crystallographic and kinetic analysis of the G12A mutant reveals a Zn2+ specificity switch suggesting a direct interaction between a divalent metal ion and the purine at position 12. The metal ion specificity switch and the pH–rate profile of the G12A mutant suggest that the minor imino tautomer of A12 serves as the general base in the mutant ribozyme. We propose a model in which the hammerhead ribozyme rearranges prior to the cleavage reaction, positioning two divalent metal ions in the process. The first metal ion, positioned near G12, becomes directly coordinated to the O6 keto oxygen, to lower the pKa of the general base and organize the active site. The second metal ion, positioned near G10.1, bridges the N7 of G10.1 and the scissile phosphate and may participate directly in the cleavage reaction. PMID:26398724

  13. Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

    Science.gov (United States)

    Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

    2014-10-13

    Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

  14. The GRB-SLSN connection: misaligned magnetars, weak jet emergence, and observational signatures

    Science.gov (United States)

    Margalit, Ben; Metzger, Brian D.; Thompson, Todd A.; Nicholl, Matt; Sukhbold, Tuguldur

    2018-04-01

    Multiple lines of evidence support a connection between hydrogen-poor superluminous supernovae (SLSNe) and long-duration gamma-ray bursts (GRBs). Both classes of events require a powerful central energy source, usually attributed to a millisecond magnetar or an accreting black hole. The GRB-SLSN link raises several theoretical questions: What distinguishes the engines responsible for these different phenomena? Can a single engine power both a GRB and a luminous SN in the same event? We propose a unifying model for magnetar thermalization and jet formation: misalignment between the rotation (Ω) and magnetic dipole (μ) axes dissipates a fraction of the spin-down power by reconnection in the striped equatorial wind, providing a guaranteed source of `thermal' emission to power the supernova. The remaining unthermalized power energizes a relativistic jet. We show that even weak relativistic jets of luminosity ˜1046 erg s-1 can escape the expanding SN ejecta implying that escaping relativistic jets may accompany many SLSNe. We calculate the observational signature of these jets. We show that they may produce transient ultraviolet (UV) cocoon emission lasting a few hours when the jet breaks out of the ejecta surface. A longer lived optical/UV signal may originate from a mildly relativistic wind driven from the interface between the jet and the ejecta walls, which could explain the secondary early-time maximum observed in some SLSNe light curves, such as LSQ14bdq. Our scenario predicts a population of GRB from on-axis jets with extremely long durations, potentially similar to the population of `jetted-tidal disruption events', in coincidence with a small subset of SLSNe.

  15. PANCHROMATIC OBSERVATIONS OF THE TEXTBOOK GRB 110205A: CONSTRAINING PHYSICAL MECHANISMS OF PROMPT EMISSION AND AFTERGLOW

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, W. [Department of Physics, University of Michigan, 450 Church Street, Ann Arbor, MI 48109 (United States); Shen, R. F. [Department of Astronomy and Astrophysics, University of Toronto, Toronto, Ontario M5S 3H4 (Canada); Sakamoto, T. [Center for Research and Exploration in Space Science and Technology (CRESST), NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Beardmore, A. P. [Department of Physics and Astronomy, University of Leicester, Leicester LE1 7RH (United Kingdom); De Pasquale, M. [Mullard Space Science Laboratory, University College London, Holmbury Road, Holmbury St. Mary, Dorking RH5 6NT (United Kingdom); Wu, X. F.; Zhang, B. [Department of Physics and Astronomy, University of Nevada Las Vegas, Las Vegas, NV 89154 (United States); Gorosabel, J. [Instituto de Astrofisica de Andalucia (IAA-CSIC), 18008 Granada (Spain); Urata, Y. [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Sugita, S. [EcoTopia Science Institute, Nagoya University, Furo-cho, chikusa, Nagoya 464-8603 (Japan); Pozanenko, A. [Space Research Institute (IKI), 84/32 Profsoyuznaya St., Moscow 117997 (Russian Federation); Nissinen, M. [Taurus Hill Observatory, Haerkaemaeentie 88, 79480 Kangaslampi (Finland); Sahu, D. K. [CREST, Indian Institute of Astrophysics, Koramangala, Bangalore 560034 (India); Im, M. [Center for the Exploration of the Origin of the Universe, Department of Physics and Astronomy, FPRD, Seoul National University, Shillim-dong, San 56-1, Kwanak-gu, Seoul (Korea, Republic of); Ukwatta, T. N. [Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824 (United States); Andreev, M. [Terskol Branch of Institute of Astronomy of RAS, Kabardino-Balkaria Republic 361605 (Russian Federation); Klunko, E., E-mail: zwk@umich.edu, E-mail: rfshen@astro.utoronto.ca, E-mail: zhang@physics.unlv.edu [Institute of Solar-Terrestrial Physics, Lermontov St., 126a, Irkutsk 664033 (Russian Federation); and others

    2012-06-01

    We present a comprehensive analysis of a bright, long-duration (T{sub 90} {approx} 257 s) GRB 110205A at redshift z = 2.22. The optical prompt emission was detected by Swift/UVOT, ROTSE-IIIb, and BOOTES telescopes when the gamma-ray burst (GRB) was still radiating in the {gamma}-ray band, with optical light curve showing correlation with {gamma}-ray data. Nearly 200 s of observations were obtained simultaneously from optical, X-ray, to {gamma}-ray (1 eV to 5 MeV), which makes it one of the exceptional cases to study the broadband spectral energy distribution during the prompt emission phase. In particular, we clearly identify, for the first time, an interesting two-break energy spectrum, roughly consistent with the standard synchrotron emission model in the fast cooling regime. Shortly after prompt emission ({approx}1100 s), a bright (R = 14.0) optical emission hump with very steep rise ({alpha} {approx} 5.5) was observed, which we interpret as the reverse shock (RS) emission. It is the first time that the rising phase of an RS component has been closely observed. The full optical and X-ray afterglow light curves can be interpreted within the standard reverse shock (RS) + forward shock (FS) model. In general, the high-quality prompt and afterglow data allow us to apply the standard fireball model to extract valuable information, including the radiation mechanism (synchrotron), radius of prompt emission (R{sub GRB} {approx} 3 Multiplication-Sign 10{sup 13} cm), initial Lorentz factor of the outflow ({Gamma}{sub 0} {approx} 250), the composition of the ejecta (mildly magnetized), the collimation angle, and the total energy budget.

  16. Measuring the beaming angle of GRB 030329 by fitting the rebrightenings in its multiband afterglow

    International Nuclear Information System (INIS)

    Deng Wei; Huang Yongfeng; Kong Siwei

    2010-01-01

    Multiple rebrightenings have been observed in the multiband afterglow of GRB 030329. In particular, a marked and quick rebrightening occurred at about t ∼ 1.2 x 10 5 s. Energy injection from late and slow shells seems to be the best interpretation for these rebrightenings. Usually it is assumed that the energy is injected into the whole external shock. However, in the case of GRB 030329, the rebrightenings are so quick that the usual consideration fails to give a satisfactory fit to the observed light curves. Actually, since these late/slow shells freely coast in the wake of the external shock, they should be cold and may not expand laterally. The energy injection then should only occur at the central region of the external shock. Considering this effect, we numerically re-fit the quick rebrightenings observed in GRB 030329. By doing this, we were able to derive the beaming angle of the energy injection process. Our result, with a relative residual of only 5% - 10% during the major rebrightening, is better than any previous modeling. The derived energy injection angle is about 0.035. We assume that these late shells are ejected by the central engine via the same mechanism as those early shells that produce the prompt gamma-ray burst. The main difference is that their velocities are much slower, so that they catch up with the external shock relatively late and are manifested as the observed quick rebrightenings. If this were true, then the derived energy injection angle can give a good measure of the beaming angle of the prompt γ-ray emission. Our study may hopefully provide a novel method to measure the beaming angle of gamma-ray bursts. (research papers)

  17. On the mass-metallicity relation, velocity dispersion and gravitational well depth of GRB host galaxies

    DEFF Research Database (Denmark)

    Arabsalmani, Maryam; Møller, Palle; Fynbo, Johan P. U.

    2015-01-01

    -DLA samples and compare the measured stellar masses for the four hosts where stellar masses have been determined from SED fits. We find excellent agreement and conclude that, on basis of all available data and tests, long duration GRB-DLA hosts and intervening QSO-DLAs are consistent with being drawn from...... away from the metallicity in the centre of the galaxy, second the path of the sightline through different parts of the potential well of the dark matter halo will cause different velocity fields to be sampled. We report evidence suggesting that this second effect may have been detected....

  18. THE AFTERGLOW AND ULIRG HOST GALAXY OF THE DARK SHORT GRB 120804A

    International Nuclear Information System (INIS)

    Berger, E.; Zauderer, B. A.; Margutti, R.; Laskar, T.; Fong, W.; Chornock, R.; Dupuy, T. J.; Levan, A.; Tunnicliffe, R. L.; Mangano, V.; Fox, D. B.; Tanvir, N. R.; Menten, K. M.; Hjorth, J.; Roth, K.

    2013-01-01

    We present the optical discovery and subarcsecond optical and X-ray localization of the afterglow of the short GRB 120804A, as well as optical, near-IR, and radio detections of its host galaxy. X-ray observations with Swift/XRT, Chandra, and XMM-Newton extending to δt ≈ 19 days reveal a single power-law decline. The optical afterglow is faint, and comparison to the X-ray flux indicates that GRB 120804A is ''dark'', with a rest-frame extinction of A host V ≈ 2.5 mag (at z = 1.3). The intrinsic neutral hydrogen column density inferred from the X-ray spectrum, N H, i nt (z = 1.3) ≈ 2 × 10 22 cm –2 , is commensurate with the large extinction. The host galaxy exhibits red optical/near-IR colors. Equally important, JVLA observations at ≈0.9-11 days reveal a constant flux density of F ν (5.8 GHz) = 35 ± 4 μJy and an optically thin spectrum, unprecedented for GRB afterglows, but suggestive instead of emission from the host galaxy. The optical/near-IR and radio fluxes are well fit with the scaled spectral energy distribution of the local ultraluminous infrared galaxy (ULIRG) Arp 220 at z ≈ 1.3, with a resulting star formation rate of x ≈ 300 M ☉ yr –1 . The inferred extinction and small projected offset (2.2 ± 1.2 kpc) are also consistent with the ULIRG scenario, as is the presence of a companion galaxy at the same redshift and with a separation of about 11 kpc. The limits on radio afterglow emission, in conjunction with the observed X-ray and optical emission, require a circumburst density of n ∼ 10 –3 cm –3 , an isotropic-equivalent energy scale of E γ, i so ≈ E K, i so ≈ 7 × 10 51 erg, and a jet opening angle of θ j ∼> 11°. The expected fraction of luminous infrared galaxies in the short GRB host sample is ∼0.01 and ∼0.25 (for pure stellar mass and star formation weighting, respectively). Thus, the observed fraction of two events in about 25 hosts (GRBs 120804A and 100206A) appears to support our previous conclusion that short

  19. X-ray spectral components observed in the afterglow of GRB 130925A

    DEFF Research Database (Denmark)

    Bellm, Eric C.; Barrière, Nicolas M.; Bhalerao, Varun

    2014-01-01

    We have identified spectral features in the late-time X-ray afterglow of the unusually long, slow-decaying GRB 130925A using NuSTAR, Swift/X-Ray Telescope, and Chandra. A spectral component in addition to an absorbed power law is required at >4σ significance, and its spectral shape varies between...... two observation epochs at 2 × 105 and 106 s after the burst. Several models can fit this additional component, each with very different physical implications. A broad, resolved Gaussian absorption feature of several keV width improves the fit, but it is poorly constrained in the second epoch...

  20. Strong Constraints on Cosmological Gravity from GW170817 and GRB 170817A

    Science.gov (United States)

    Baker, T.; Bellini, E.; Ferreira, P. G.; Lagos, M.; Noller, J.; Sawicki, I.

    2017-12-01

    The detection of an electromagnetic counterpart (GRB 170817A) to the gravitational-wave signal (GW170817) from the merger of two neutron stars opens a completely new arena for testing theories of gravity. We show that this measurement allows us to place stringent constraints on general scalar-tensor and vector-tensor theories, while allowing us to place an independent bound on the graviton mass in bimetric theories of gravity. These constraints severely reduce the viable range of cosmological models that have been proposed as alternatives to general relativistic cosmology.

  1. VizieR Online Data Catalog: GRB 160509A VLA monitoring campain results (Laskar+, 2016)

    Science.gov (United States)

    Laskar, T.; Alexander, K. D.; Berger, E.; Fong, W.-F.; Margutti, R.; Shivvers, I.; Williams, P. K. G.; Kopac, D.; Kobayashi, S.; Mundell, C.; Gomboc, A.; Zheng, W.; Menten, K. M.; Graham, M. L.; Filippenko, A. V.

    2017-04-01

    GRB 160509A was discovered by the Fermi LAT on 2016 May 09 at 08:59:04.36 UTC (Longo+ 2016GCN..19403...1L). We observed the afterglow with the VLA starting at 0.36 days. We tracked the flux density of the afterglow over multiple epochs spanning 1.2-33.5GHz, using 3C48, 3C286, and 3C147 as flux and bandpass calibrators, and J2005+7752 as the gain calibrator. Our VLA observations spanning 0.36-20 days after the burst clearly reveal the presence of multiple spectral components in the radio afterglow. (1 data file).

  2. Single-stranded DNA cleavage by divergent CRISPR-Cas9 enzymes

    Science.gov (United States)

    Ma, Enbo; Harrington, Lucas B.; O’Connell, Mitchell R.; Zhou, Kaihong; Doudna, Jennifer A.

    2015-01-01

    Summary Double-stranded DNA (dsDNA) cleavage by Cas9 is a hallmark of type II CRISPR-Cas immune systems. Cas9–guide RNA complexes recognize 20-base-pair sequences in DNA and generate a site-specific double-strand break, a robust activity harnessed for genome editing. DNA recognition by all studied Cas9 enzymes requires a protospacer adjacent motif (PAM) next to the target site. We show that Cas9 enzymes from evolutionarily divergent bacteria can recognize and cleave single-stranded DNA (ssDNA) by an RNA-guided, PAM-independent recognition mechanism. Comparative analysis shows that in contrast to the type II-A S. pyogenes Cas9 that is widely used for genome engineering, the smaller type II-C Cas9 proteins have limited dsDNA binding and unwinding activity and promiscuous guide-RNA specificity. These results indicate that inefficiency of type II-C Cas9 enzymes for genome editing results from a limited ability to cleave dsDNA, and suggest that ssDNA cleavage was an ancestral function of the Cas9 enzyme family. PMID:26545076

  3. The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single-Molecule FRET.

    Science.gov (United States)

    Yang, Mengyi; Peng, Sijia; Sun, Ruirui; Lin, Jingdi; Wang, Nan; Chen, Chunlai

    2018-01-09

    Off-target binding and cleavage by Cas9 pose major challenges in its application. How the conformational dynamics of Cas9 govern its nuclease activity under on- and off-target conditions remains largely unknown. Here, using intra-molecular single-molecule fluorescence resonance energy transfer measurements, we revealed that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits among three major conformational states, mainly reflecting significant conformational mobility of the catalytic HNH domain. We also uncovered surprising long-range allosteric communication between the HNH domain and the RNA/DNA heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic site, which demonstrated that a unique proofreading mechanism served as the last checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the allosteric communication and proofreading step. Modulating interactions between Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these sites provides an alternative route to improve and optimize the CRISPR/Cas9 toolbox. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes

    Science.gov (United States)

    Liu, Ming; Lara-Lemus, Roberto; Shan, Shu-ou; Wright, Jordan; Haataja, Leena; Barbetti, Fabrizio; Guo, Huan; Larkin, Dennis; Arvan, Peter

    2012-01-01

    Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an improper site, producing two subpopulations of molecules. Both show impaired oxidative folding and are retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER exit of coexpressed wild-type proinsulin, accounting for its dominant-negative behavior. Upon increased expression of ER–oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative folding of wild-type proinsulin improves, accelerating its ER export and increasing wild-type insulin production. We conclude that the efficiency of SP cleavage is linked to the oxidation of (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of the mutant as well as that of coexpressed wild-type proinsulin. Improving oxidative folding of wild-type proinsulin may provide a feasible way to rescue insulin production in patients with MIDY. PMID:22357960

  5. TRAIL-induced cleavage and inactivation of SPAK sensitizes cells to apoptosis

    International Nuclear Information System (INIS)

    Polek, Tara C.; Talpaz, Moshe; Spivak-Kroizman, Taly R.

    2006-01-01

    Ste20-related proline-alanine-rich kinase (SPAK) has been linked to various cellular processes, including proliferation, differentiation, and ion transport regulation. Recently, we showed that SPAK mediates signaling by the TNF receptor, RELT. The presence of a caspase cleavage site in SPAK prompted us to study its involvement in apoptotic signaling induced by another TNF member, TRAIL. We show that TRAIL stimulated caspase 3-like proteases that cleaved SPAK at two distinct sites. Cleavage had little effect on the activity of SPAK but removed its substrate-binding domain. In addition, TRAIL reduced the activity of SPAK in HeLa cells in a caspase-independent manner. Thus, TRAIL inhibited SPAK by two mechanisms: activation of caspases, which removed its substrate-binding domain, and caspase-independent down-regulation of SPAK activity. Furthermore, reducing the amount of SPAK by siRNA increased the sensitivity of HeLa cells to TRAIL-induced apoptosis. Thus, TRAIL down-regulation of SPAK is an important event that enhances its apoptotic effects

  6. DNA Cleavage Activity of Diazonium Salts: Chemical Nucleases

    OpenAIRE

    KIZIL, Murat

    2014-01-01

    4-Fenoldiazonium tetrafluoroborate and 4-benzoicaciddiazonium tetrafluoroborate was prepared and was shown to be an effective DNA cleavage agent in the presence of the 1-electron donor copper(II) chloride. Its mechanism involves the generation of the aryl radical cleaving DNA by hydrogen atom abstraction from deoxyribose sugar.

  7. Fe-Catalyzed Oxidative Cleavage of Unsaturated Fatty Acids

    NARCIS (Netherlands)

    Spannring, P.

    2013-01-01

    The oxidative cleavage of unsaturated fatty acids into aldehydes or carboxylic acids gives access to valuable products. The products can be used as chemical building blocks, as emulsifiers or in the paint or polymer industry. Ozonolysis is applied industrially to cleave the fatty acid oleic acid

  8. Kinetics of phycocyanobilin cleavage from C-phycocyanin by methanolysis

    DEFF Research Database (Denmark)

    Malwade, Chandrakant Ramkrishna; Roda Serrat, Maria Cinta; Christensen, Knud Villy

    2016-01-01

    Phycocyanobilin (PCB) is an important linear tetrapyrrolic molecule for food as well as pharmaceutical industry. It is obtained from blue-green algae, where it is attached covalently to phycobiliproteins (C-PC and APC) present in the light harvesting complexes. In this work, cleavage of PCB from...

  9. Cell-surface acceleration of urokinase-catalyzed receptor cleavage

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Ploug, M; Behrendt, N

    1997-01-01

    by a prior incubation of the cells with uPA inactivated by diisopropyl fluorophosphate, demonstrating a requirement for specific receptor binding of the active uPA to obtain the high-efficiency cleavage of cell-bound uPAR. Furthermore, amino-terminal sequence analysis revealed that uPAR(2+3), purified from U...

  10. High-resolution characterization of sequence signatures due to non-random cleavage of cell-free DNA.

    Science.gov (United States)

    Chandrananda, Dineika; Thorne, Natalie P; Bahlo, Melanie

    2015-06-17

    High-throughput sequencing of cell-free DNA fragments found in human plasma has been used to non-invasively detect fetal aneuploidy, monitor organ transplants and investigate tumor DNA. However, many biological properties of this extracellular genetic material remain unknown. Research that further characterizes circulating DNA could substantially increase its diagnostic value by allowing the application of more sophisticated bioinformatics tools that lead to an improved signal to noise ratio in the sequencing data. In this study, we investigate various features of cell-free DNA in plasma using deep-sequencing data from two pregnant women (>70X, >50X) and compare them with matched cellular DNA. We utilize a descriptive approach to examine how the biological cleavage of cell-free DNA affects different sequence signatures such as fragment lengths, sequence motifs at fragment ends and the distribution of cleavage sites along the genome. We show that the size distributions of these cell-free DNA molecules are dependent on their autosomal and mitochondrial origin as well as the genomic location within chromosomes. DNA mapping to particular microsatellites and alpha repeat elements display unique size signatures. We show how cell-free fragments occur in clusters along the genome, localizing to nucleosomal arrays and are preferentially cleaved at linker regions by correlating the mapping locations of these fragments with ENCODE annotation of chromatin organization. Our work further demonstrates that cell-free autosomal DNA cleavage is sequence dependent. The region spanning up to 10 positions on either side of the DNA cleavage site show a consistent pattern of preference for specific nucleotides. This sequence motif is present in cleavage sites localized to nucleosomal cores and linker regions but is absent in nucleosome-free mitochondrial DNA. These background signals in cell-free DNA sequencing data stem from the non-random biological cleavage of these fragments. This

  11. Cleavage of influenza RNA by using a human PUF-based artificial RNA-binding protein–staphylococcal nuclease hybrid

    International Nuclear Information System (INIS)

    Mori, Tomoaki; Nakamura, Kento; Masaoka, Keisuke; Fujita, Yusuke; Morisada, Ryosuke; Mori, Koichi; Tobimatsu, Takamasa; Sera, Takashi

    2016-01-01

    Various viruses infect animals and humans and cause a variety of diseases, including cancer. However, effective methodologies to prevent virus infection have not yet been established. Therefore, development of technologies to inactivate viruses is highly desired. We have already demonstrated that cleavage of a DNA virus genome was effective to prevent its replication. Here, we expanded this methodology to RNA viruses. In the present study, we used staphylococcal nuclease (SNase) instead of the PIN domain (PilT N-terminus) of human SMG6 as an RNA-cleavage domain and fused the SNase to a human Pumilio/fem-3 binding factor (PUF)-based artificial RNA-binding protein to construct an artificial RNA restriction enzyme with enhanced RNA-cleavage rates for influenzavirus. The resulting SNase-fusion nuclease cleaved influenza RNA at rates 120-fold greater than the corresponding PIN-fusion nuclease. The cleaving ability of the PIN-fusion nuclease was not improved even though the linker moiety between the PUF and RNA-cleavage domain was changed. Gel shift assays revealed that the RNA-binding properties of the PUF derivative used was not as good as wild type PUF. Improvement of the binding properties or the design method will allow the SNase-fusion nuclease to cleave an RNA target in mammalian animal cells and/or organisms. - Highlights: • A novel RNA restriction enzyme using SNase was developed tor cleave viral RNA. • Our enzyme cleaved influenza RNA with rates >120-fold higher rates a PIN-fusion one. • Our artificial enzyme with the L5 linker showed the highest RNA cleavage rate. • Our artificial enzyme site-selectively cleaved influenza RNA in vitro.

  12. Cleavage of nicotinamide adenine dinucleotide by the ribosome-inactivating protein from Momordica charantia.

    Science.gov (United States)

    Vinkovic, M; Dunn, G; Wood, G E; Husain, J; Wood, S P; Gill, R

    2015-09-01

    The interaction of momordin, a type 1 ribosome-inactivating protein from Momordica charantia, with NADP(+) and NADPH has been investigated by X-ray diffraction analysis of complexes generated by co-crystallization and crystal soaking. It is known that the proteins of this family readily cleave the adenine-ribose bond of adenosine and related nucleotides in the crystal, leaving the product, adenine, bound to the enzyme active site. Surprisingly, the nicotinamide-ribose bond of oxidized NADP(+) is cleaved, leaving nicotinamide bound in the active site in the same position but in a slightly different orientation to that of the five-membered ring of adenine. No binding or cleavage of NADPH was observed at pH 7.4 in these experiments. These observations are in accord with current views of the enzyme mechanism and may contribute to ongoing searches for effective inhibitors.

  13. ESTIMATING LONG GRB JET OPENING ANGLES AND REST-FRAME ENERGETICS

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, Adam [Space Science Office, VP62, NASA/Marshall Space Flight Center, Huntsville, AL 35812 (United States); Connaughton, Valerie [Science and Technology Institute, Universities Space Research Association, Huntsville, AL 35805 (United States); Briggs, Michael S.; Burns, Eric, E-mail: adam.m.goldstein@nasa.gov [Center for Space Plasma and Aeronomic Research, University of Alabama in Huntsville, 320 Sparkman Drive, Huntsville, AL 35899 (United States)

    2016-02-10

    We present a method to estimate the jet opening angles of long duration gamma-ray bursts (GRBs) using the prompt gamma-ray energetics and an inversion of the Ghirlanda relation, which is a correlation between the time-integrated peak energy of the GRB prompt spectrum and the collimation-corrected energy in gamma-rays. The derived jet opening angles using this method and detailed assumptions match well with the corresponding inferred jet opening angles obtained when a break in the afterglow is observed. Furthermore, using a model of the predicted long GRB redshift probability distribution observable by the Fermi Gamma-ray Burst Monitor (GBM), we estimate the probability distributions for the jet opening angle and rest-frame energetics for a large sample of GBM GRBs for which the redshifts have not been observed. Previous studies have only used a handful of GRBs to estimate these properties due to the paucity of observed afterglow jet breaks, spectroscopic redshifts, and comprehensive prompt gamma-ray observations, and we potentially expand the number of GRBs that can be used in this analysis by more than an order of magnitude. In this analysis, we also present an inferred distribution of jet breaks which indicates that a large fraction of jet breaks are not observable with current instrumentation and observing strategies. We present simple parameterizations for the jet angle, energetics, and jet break distributions so that they may be used in future studies.

  14. Infrared Emission from Kilonovae: The Case of the Nearby Short Hard Burst GRB 160821B

    Energy Technology Data Exchange (ETDEWEB)

    Kasliwal, Mansi M.; Lau, Ryan M. [Division of Physics, Mathematics and Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Korobkin, Oleg; Wollaeger, Ryan; Fryer, Christopher L. [Computational Methods Group (CCS-2), Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, NM, 87545 (United States)

    2017-07-10

    We present constraints on Ks-band emission from one of the nearest short hard gamma-ray bursts, GRB 160821B, at z = 0.16, at three epochs. We detect a red relativistic afterglow from the jetted emission in the first epoch but do not detect any excess kilonova emission in the second two epochs. We compare upper limits obtained with Keck I/MOSFIRE to multi-dimensional radiative transfer models of kilonovae, that employ composition-dependent nuclear heating and LTE opacities of heavy elements. We discuss eight models that combine toroidal dynamical ejecta and two types of wind and one model with dynamical ejecta only. We also discuss simple, empirical scaling laws of predicted emission as a function of ejecta mass and ejecta velocity. Our limits for GRB 160821B constrain the ejecta mass to be lower than 0.03 M {sub ⊙} for velocities greater than 0.1 c. At the distance sensitivity range of advanced LIGO, similar ground-based observations would be sufficiently sensitive to the full range of predicted model emission including models with only dynamical ejecta. The color evolution of these models shows that I – K color spans 7–16 mag, which suggests that even relatively shallow infrared searches for kilonovae could be as constraining as optical searches.

  15. DETECTION OF GAMMA-RAY POLARIZATION IN PROMPT EMISSION OF GRB 100826A

    Energy Technology Data Exchange (ETDEWEB)

    Yonetoku, Daisuke; Murakami, Toshio; Sakashita, Tomonori; Morihara, Yoshiyuki; Takahashi, Takuya; Fujimoto, Hirofumi; Kodama, Yoshiki [College of Science and Engineering, School of Mathematics and Physics, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192 (Japan); Gunji, Shuichi; Toukairin, Noriyuki [Department of Physics, Faculty of Science, Yamagata University, 1-4-12, Koshirakawa, Yamagata, Yamagata 990-8560 (Japan); Mihara, Tatehiro [Cosmic Radiation Laboratory, RIKEN, 2-1, Hirosawa, Wako City, Saitama 351-0198 (Japan); Toma, Kenji [Department of Earth and Space Science, Osaka University, Toyonaka 560-0043 (Japan); Kubo, Shin, E-mail: yonetoku@astro.s.kanazawa-u.ac.jp [Clear Pulse Co. Ltd., 6-25-17, Chuo, Ohta-ku, Tokyo 143-0024 (Japan); Institute of Space and Astronautical Science (ISAS), Japan Aerospace Exploration Agency (JAXA), 3-1-1, Yoshinodai, Sagamihara, Kanagawa 229-8510 (Japan)

    2011-12-20

    We report the polarization measurement in prompt {gamma}-ray emission of GRB 100826A with the Gamma-Ray Burst Polarimeter on board the small solar-power-sail demonstrator IKAROS. We detected the firm change of polarization angle (PA) during the prompt emission with 99.9% (3.5{sigma}) confidence level, and the average polarization degree ({Pi}) of 27% {+-} 11% with 99.4% (2.9{sigma}) confidence level. Here the quoted errors are given at 1{sigma} confidence level for the two parameters of interest. The systematic errors have been carefully included in this analysis, unlike other previous reports. Such a high {Pi} can be obtained in several emission models of gamma-ray bursts (GRBs), including synchrotron and photospheric models. However, it is difficult to explain the observed significant change of PA within the framework of axisymmetric jet as considered in many theoretical works. The non-axisymmetric (e.g., patchy) structures of the magnetic fields and/or brightness inside the relativistic jet are therefore required within the observable angular scale of {approx}{Gamma}{sup -1}. Our observation strongly indicates that the polarization measurement is a powerful tool to constrain the GRB production mechanism, and more theoretical works are needed to discuss the data in more detail.

  16. GIANT X-RAY BUMP IN GRB 121027A: EVIDENCE FOR FALL-BACK DISK ACCRETION

    Energy Technology Data Exchange (ETDEWEB)

    Wu Xuefeng [Purple Mountain Observatory, Chinese Academy of Sciences, Nanjing 210008 (China); Hou Shujin [Department of Astronomy and Institute of Theoretical Physics and Astrophysics, Xiamen University, Xiamen, Fujian 361005 (China); Lei Weihua, E-mail: xfwu@pmo.ac.cn, E-mail: leiwh@hust.edu.cn [School of Physics, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2013-04-20

    A particularly interesting discovery in observations of GRB 121027A is that of a giant X-ray bump detected by the Swift/X-Ray Telescope. The X-ray afterglow re-brightens sharply at {approx}10{sup 3} s after the trigger by more than two orders of magnitude in less than 200 s. This X-ray bump lasts for more than 10{sup 4} s. It is quite different from typical X-ray flares. In this Letter we propose a fall-back accretion model to interpret this X-ray bump within the context of the collapse of a massive star for a long-duration gamma-ray burst. The required fall-back radius of {approx}3.5 Multiplication-Sign 10{sup 10} cm and mass of {approx}0.9-2.6 M{sub Sun} imply that a significant part of the helium envelope should survive through the mass loss during the last stage of the massive progenitor of GRB 121027A.

  17. Constraining Anisotropic Lorentz Violation via the Spectral-lag Transition of GRB 160625B

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Jun-Jie; Wu, Xue-Feng; Shao, Lang [Purple Mountain Observatory, Chinese Academy of Sciences, Nanjing 210008 (China); Zhang, Bin-Bin [Instituto de Astrofísica de Andalucá (IAA-CSIC), P.O. Box 03004, E-18080 Granada (Spain); Mészáros, Peter [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Kostelecký, V. Alan, E-mail: xfwu@pmo.ac.cn, E-mail: kostelec@indiana.edu [Physics Department, Indiana University, Bloomington, IN 47405 (United States)

    2017-06-20

    Violations of Lorentz invariance can lead to an energy-dependent vacuum dispersion of light, which results in arrival-time differences of photons with different energies arising from a given transient source. In this work, direction-dependent dispersion constraints are obtained on nonbirefringent Lorentz-violating effects using the observed spectral lags of the gamma-ray burst GRB 160625B. This burst has unusually large high-energy photon statistics, so we can obtain constraints from the true spectral time lags of bunches of high-energy photons rather than from the rough time lag of a single highest-energy photon. Also, GRB 160625B is the only burst to date having a well-defined transition from positive lags to negative lags, providing a unique opportunity to distinguish Lorentz-violating effects from any source-intrinsic time lag in the emission of photons of different energy bands. Our results place comparatively robust two-sided constraints on a variety of isotropic and anisotropic coefficients for Lorentz violation, including the first bounds on Lorentz-violating effects from operators of mass dimension 10 in the photon sector.

  18. LIMITS ON OPTICAL POLARIZATION DURING THE PROMPT PHASE OF GRB 140430A

    Energy Technology Data Exchange (ETDEWEB)

    Kopac, D.; Mundell, C. G.; Arnold, D. M.; Steele, I. A.; Kobayashi, S.; Lamb, G. P.; Smith, R. J.; Virgili, F. J. [Astrophysics Research Institute, Liverpool John Moores University, 146 Brownlow Hill, Liverpool, L3 5RF (United Kingdom); Japelj, J.; Gomboc, A. [Department of Physics, Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, 1000 Ljubljana (Slovenia); Guidorzi, C.; Dichiara, S. [Department of Physics and Earth Sciences, University of Ferrara, via Saragat 1, I-44122, Ferrara (Italy); Harrison, R. M. [Department of Astrophysics, School of Physics and Astronomy, Tel Aviv University, 69978 Tel Aviv (Israel); Melandri, A. [INAF—Osservatorio Astronomico di Brera, via E. Bianchi 46, I-23807 Merate (Italy); Castro-Tirado, A. J.; Gorosabel, J.; Sánchez-Ramírez, R.; Oates, S. R. [Instituto de Astrofísica de Andalucía (IAA-CSIC), Glorieta de la Astronomia s/n, E-18008 Granada (Spain); Järvinen, A. [AIP—Leibniz-Institut für Astrophysik Potsdam, An der Sternwarte 16, D-14482 Potsdam (Germany); Jelínek, M., E-mail: drejc.kopac@fmf.uni-lj.si [ASU-CAS—Astronomical Institute of the Czech Academy of Sciences, Fričova 298, 251 65 Ondřejov (Czech Republic)

    2015-11-01

    Gamma-ray burst GRB 140430A was detected by the Swift satellite and observed promptly with the imaging polarimeter RINGO3 mounted on the Liverpool Telescope, with observations beginning while the prompt γ-ray emission was still ongoing. In this paper, we present densely sampled (10-s temporal resolution) early optical light curves (LCs) in 3 optical bands and limits to the degree of optical polarization. We compare optical, X-ray, and gamma-ray properties and present an analysis of the optical emission during a period of high-energy flaring. The complex optical LC cannot be explained merely with a combination of forward and reverse shock emission from a standard external shock, implying additional contribution of emission from internal shock dissipation. We estimate an upper limit for time averaged optical polarization during the prompt phase to be as low as P < 12% (1σ). This suggests that the optical flares and early afterglow emission in this GRB are not highly polarized. Alternatively, time averaging could mask the presence of otherwise polarized components of distinct origin at different polarization position angles.

  19. Exploring short-GRB afterglow parameter space for observations in coincidence with gravitational waves

    Science.gov (United States)

    Saleem, M.; Resmi, L.; Misra, Kuntal; Pai, Archana; Arun, K. G.

    2018-03-01

    Short duration Gamma Ray Bursts (SGRB) and their afterglows are among the most promising electromagnetic (EM) counterparts of Neutron Star (NS) mergers. The afterglow emission is broad-band, visible across the entire electromagnetic window from γ-ray to radio frequencies. The flux evolution in these frequencies is sensitive to the multidimensional afterglow physical parameter space. Observations of gravitational wave (GW) from BNS mergers in spatial and temporal coincidence with SGRB and associated afterglows can provide valuable constraints on afterglow physics. We run simulations of GW-detected BNS events and assuming that all of them are associated with a GRB jet which also produces an afterglow, investigate how detections or non-detections in X-ray, optical and radio frequencies can be influenced by the parameter space. We narrow down the regions of afterglow parameter space for a uniform top-hat jet model, which would result in different detection scenarios. We list inferences which can be drawn on the physics of GRB afterglows from multimessenger astronomy with coincident GW-EM observations.

  20. Search for gravitational waves associated with the gamma ray burst GRB030329 using the LIGO detectors

    International Nuclear Information System (INIS)

    Abbott, B.; Anderson, S.B.; Araya, M.; Armandula, H.; Asiri, F.; Barish, B.C.; Barnes, M.; Barton, M.A.; Bhawal, B.; Billingsley, G.; Black, E.; Blackburn, K.; Bogue, L.; Bork, R.; Busby, D.; Cardenas, L.; Chandler, A.; Chapsky, J.; Charlton, P.; Coyne, D.

    2005-01-01

    We have performed a search for bursts of gravitational waves associated with the very bright gamma ray burst GRB030329, using the two detectors at the LIGO Hanford Observatory. Our search covered the most sensitive frequency range of the LIGO detectors (approximately 80--2048 Hz), and we specifically targeted signals shorter than ≅150 ms. Our search algorithm looks for excess correlated power between the two interferometers and thus makes minimal assumptions about the gravitational waveform. We observed no candidates with gravitational-wave signal strength larger than a predetermined threshold. We report frequency-dependent upper limits on the strength of the gravitational waves associated with GRB030329. Near the most sensitive frequency region, around ≅250 Hz, our root-sum-square (RSS) gravitational-wave strain sensitivity for optimally polarized bursts was better than h RSS ≅6x10 -21 Hz -1/2 . Our result is comparable to the best published results searching for association between gravitational waves and gamma ray bursts

  1. A Neutron Star Binary Merger Model for GW170817/GRB 170817A/SSS17a

    Energy Technology Data Exchange (ETDEWEB)

    Murguia-Berthier, A.; Ramirez-Ruiz, E.; Kilpatrick, C. D.; Foley, R. J.; Coulter, D. A.; Pan, Y.-C.; Prochaska, J. X.; Rojas-Bravo, C.; Siebert, M. R. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Kasen, D. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Lee, W. H. [Instituto de Astronomía, Universidad Nacional Autónoma de México, Circuito Exterior, C.U., A. Postal 70-264, 04510 Cd. de México, México (Mexico); Piro, A. L.; Drout, M. R.; Madore, B. F.; Shappee, B. J.; Simon, J. D. [The Observatories of the Carnegie Institution for Science, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Rest, A. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States)

    2017-10-20

    The merging neutron star gravitational-wave event GW170817 has been observed throughout the entire electromagnetic spectrum from radio waves to γ -rays. The resulting energetics, variability, and light curves are shown to be consistent with GW170817 originating from the merger of two neutron stars, in all likelihood followed by the prompt gravitational collapse of the massive remnant. The available γ -ray, X-ray, and radio data provide a clear probe for the nature of the relativistic ejecta and the non-thermal processes occurring within, while the ultraviolet, optical, and infrared emission are shown to probe material torn during the merger and subsequently heated by the decay of freshly synthesized r -process material. The simplest hypothesis, that the non-thermal emission is due to a low-luminosity short γ -ray burst (sGRB), seems to agree with the present data. While low-luminosity sGRBs might be common, we show here that the collective prompt and multi-wavelength observations are also consistent with a typical, powerful sGRB seen off-axis. Detailed follow-up observations are thus essential before we can place stringent constraints on the nature of the relativistic ejecta in GW170817.

  2. LIMITS ON OPTICAL POLARIZATION DURING THE PROMPT PHASE OF GRB 140430A

    International Nuclear Information System (INIS)

    Kopac, D.; Mundell, C. G.; Arnold, D. M.; Steele, I. A.; Kobayashi, S.; Lamb, G. P.; Smith, R. J.; Virgili, F. J.; Japelj, J.; Gomboc, A.; Guidorzi, C.; Dichiara, S.; Harrison, R. M.; Melandri, A.; Castro-Tirado, A. J.; Gorosabel, J.; Sánchez-Ramírez, R.; Oates, S. R.; Järvinen, A.; Jelínek, M.

    2015-01-01

    Gamma-ray burst GRB 140430A was detected by the Swift satellite and observed promptly with the imaging polarimeter RINGO3 mounted on the Liverpool Telescope, with observations beginning while the prompt γ-ray emission was still ongoing. In this paper, we present densely sampled (10-s temporal resolution) early optical light curves (LCs) in 3 optical bands and limits to the degree of optical polarization. We compare optical, X-ray, and gamma-ray properties and present an analysis of the optical emission during a period of high-energy flaring. The complex optical LC cannot be explained merely with a combination of forward and reverse shock emission from a standard external shock, implying additional contribution of emission from internal shock dissipation. We estimate an upper limit for time averaged optical polarization during the prompt phase to be as low as P < 12% (1σ). This suggests that the optical flares and early afterglow emission in this GRB are not highly polarized. Alternatively, time averaging could mask the presence of otherwise polarized components of distinct origin at different polarization position angles

  3. A Reverse Shock and Unusual Radio Properties in GRB 160625B

    Science.gov (United States)

    Alexander, K. D.; Laskar, T.; Berger, E.; Guidorzi, C.; Dichiara, S.; Fong, W.; Gomboc, A.; Kobayashi, S.; Kopac, D.; Mundell, C. G.; Tanvir, N. R.; Williams, P. K. G.

    2017-10-01

    We present multi-wavelength observations and modeling of the exceptionally bright long γ-ray burst GRB 160625B. The optical and X-ray data are well fit by synchrotron emission from a collimated blastwave with an opening angle of {θ }j≈ 3\\buildrel{\\circ}\\over{.} 6 and kinetic energy of {E}K≈ 2× {10}51 erg, propagating into a low-density (n≈ 5× {10}-5 cm-3) medium with a uniform profile. The forward shock is sub-dominant in the radio band; instead, the radio emission is dominated by two additional components. The first component is consistent with emission from a reverse shock, indicating an initial Lorentz factor of {{{Γ }}}0≳ 100 and an ejecta magnetization of {R}B≈ 1{--}100. The second component exhibits peculiar spectral and temporal evolution and is most likely the result of scattering of the radio emission by the turbulent Milky Way interstellar medium (ISM). Such scattering is expected in any sufficiently compact extragalactic source and has been seen in GRBs before, but the large amplitude and long duration of the variability seen here are qualitatively more similar to extreme scattering events previously observed in quasars, rather than normal interstellar scintillation effects. High-cadence, broadband radio observations of future GRBs are needed to fully characterize such effects, which can sensitively probe the properties of the ISM and must be taken into account before variability intrinsic to the GRB can be interpreted correctly.

  4. Novel nonphosphorylated peptides with conserved sequences selectively bind to Grb7 SH2 domain with affinity comparable to its phosphorylated ligand.

    Directory of Open Access Journals (Sweden)

    Dan Zhang

    Full Text Available The Grb7 (growth factor receptor-bound 7 protein, a member of the Grb7 protein family, is found to be highly expressed in such metastatic tumors as breast cancer, esophageal cancer, liver cancer, etc. The src-homology 2 (SH2 domain in the C-terminus is reported to be mainly involved in Grb7 signaling pathways. Using the random peptide library, we identified a series of Grb7 SH2 domain-binding nonphosphorylated peptides in the yeast two-hybrid system. These peptides have a conserved GIPT/K/N sequence at the N-terminus and G/WD/IP at the C-terminus, and the region between the N-and C-terminus contains fifteen amino acids enriched with serines, threonines and prolines. The association between the nonphosphorylated peptides and the Grb7 SH2 domain occurred in vitro and ex vivo. When competing for binding to the Grb7 SH2 domain in a complex, one synthesized nonphosphorylated ligand, containing the twenty-two amino acid-motif sequence, showed at least comparable affinity to the phosphorylated ligand of ErbB3 in vitro, and its overexpression inhibited the proliferation of SK-BR-3 cells. Such nonphosphorylated peptides may be useful for rational design of drugs targeted against cancers that express high levels of Grb7 protein.

  5. Cyclic phosphopeptides for interference with Grb2 SH2 domain signal transduction prepared by ring-closing metathesis and phosphorylation

    NARCIS (Netherlands)

    Dekker, Frank J; de Mol, Nico J; Fischer, Marcel J E; Kemmink, Johan; Liskamp, Rob M J; Dekker, Frank

    2003-01-01

    Cyclic phosphopeptides were prepared using ring-closing metathesis followed by phosphorylation. These cyclic phosphopeptides were designed to interact with the SH2 domain of Grb2, which is a signal transduction protein of importance as a target for antiproliferative drug development. Binding of

  6. INTEGRAL and XMM-Newton observations of the low-luminosity and X-ray-rich burst GRB 040223

    Energy Technology Data Exchange (ETDEWEB)

    McGlynn, S.; Hanlon, L.; Foley, S. [College Univ., Dublin (Iran, Islamic Republic of). Department of Experimental Physics; McBreen, S. [ESTEC, Noordwijk (Netherlands). Astrophysics Mission Division, RSSD of ESA; Moran, L. [Southampton Univ., Southampton (United Kingdom). School of Physics and Astronomy; Preece, R. [Alabama Univ., Huntsville (United States); Kienlin, A. von [Max-Planck-Institut fur extraterrestrische Physik, Garching (Germany); Williams, O.R. [SCI-SDG, Noordwijk (Netherlands). Science Operation and Data Systems Division of ESA-ESTEC

    2005-07-15

    GRB 040223 was observed by INTEGRAL and XMM-Newton. GRB 040223 has a peak flux of (1.6{+-}0.13) x 10{sup -8} ergs cm{sup -2} s{sup -1}, a fluence of (4.4{+-}0.4) x 10{sup -7} ergs cm{sup -2} and a steep photon power law index of -2.3{+-}0.2, in the energy range 20-200 keV. The steep spectrum implies it is an X-ray-rich GRB with emission up to 200 keV and E{sub peak} < 20 keV. If E{sub peak} is < 10 keV, it would qualify as an X-ray flash with high-energy emission. The X-ray data has a spectral index {beta}{sub x} = -1.7{+-}0.2, a temporal decay of t{sup -0.75{+-}}{sup 0.25} and a large column density of 1.8 x 10{sup 22} cm{sup -2}. The luminosity-lag relationship was used to obtain a redshift z 0.1{sub -0.02}{sup +0.04}. The isotropic energy radiated in {gamma}-rays and X-ray luminosity after 10 hours are factors of 1000 and 100 less than classical GRBs. GRB 040223 is consistent with the extrapolation of the Amati relation into the region that includes XRF 030723 and XRF 020903.

  7. Preliminary crystallographic characterization of the Grb2 SH2 domain in complex with a FAK-derived phosphotyrosyl peptide

    International Nuclear Information System (INIS)

    Chen, Hsiao-Hsin; Chen, Cuei-Wen; Chang, Yu-Yung; Shen, Tang-Long; Hsu, Chun-Hua

    2010-01-01

    Crystals of the Grb2 SH2 domain in complex with a phosphotyrosyl peptide corresponding to residues 921–930 of focal adhesion kinase (FAK) have been obtained using the sitting-drop vapour-diffusion technique. Data have been collected to 2.49 Å resolution. Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein with a single SH2 domain that specifically binds to focal adhesion kinase (FAK) when residue Tyr925 of FAK is phosphorylated. The Grb2–FAK interaction is associated with cellular integrin-activated signal transduction events leading to the activation of the Ras-MAPK pathway. Crystals of the Grb2 SH2 domain in complex with a phosphopeptide corresponding to residues 921–930 of FAK have been obtained using the sitting-drop vapour-diffusion technique. The crystals belonged to space group P3 1 21, with unit-cell parameters a = b = 102.7, c = 127.6 Å, α = β = 90.0, γ = 120.0°. A diffraction data set was collected from a flash-cooled crystal at 100 K to 2.49 Å resolution using synchrotron radiation. Structure determination by molecular replacement and analysis of the detailed structure of the complex are currently in progress

  8. GRB 080517: a local, low-luminosity gamma-ray burst in a dusty galaxy at z = 0.09

    NARCIS (Netherlands)

    Stanway, E.R.; Levan, A.J.; Tanvir, N.; Wiersema, K.; van der Horst, A.; Mundell, C.G.; Guidorzi, C.

    2015-01-01

    We present an analysis of the photometry and spectroscopy of the host galaxy of Swift-detected GRB 080517. From our optical spectroscopy, we identify a redshift of z = 0.089 ± 0.003, based on strong emission lines, making this a rare example of a very local, low-luminosity, long gamma-ray burst. The

  9. A recombined fusion protein PTD-Grb2-SH2 inhibits the proliferation of breast cancer cells in vitro.

    Science.gov (United States)

    Yin, Jikai; Cai, Zhongliang; Zhang, Li; Zhang, Jian; He, Xianli; Du, Xilin; Wang, Qing; Lu, Jianguo

    2013-03-01

    The growth factor receptor bound protein 2 (Grb2) is one of the affirmative targets for cancer therapy, especially for breast cancer. In this study, we hypothesized the Src-homology 2 (SH2) domain in Grb2 may serve as a competitive protein-binding agent to interfere with the proliferation of breast cancer cells in vitro. We designed, constructed, expressed and purified a novel fusion protein containing the protein transduction domain (PTD) and Grb2-SH2 domain (we named it after PTD-Grb2-SH2). An immunofluorescence assay was used to investigate the location of PTD-Grb2-SH2 in cells. MTT assay and EdU experiments were applied to detect the proliferation of breast cancer cells. The ultra-structure was observed using transmission electron microscopy. Flow cytometry was used to determine the cytotoxicity of PTD-Grb2-SH2 on cell proliferation. We successfully obtained the PTD-Grb2-SH2 fusion protein in soluble form using a prokaryotic expression system. The new fusion protein successfully passed through both the cellular and nuclear membranes of breast cancer cells. The MTT assay showed that PTD-Grb2-SH2 exhibited significant toxicity to breast cancer cells in a dose- and time-dependent manner in vitro. EdU identified the decreased proliferation rates in treated MDA-MB-231 and SK-BR-3 cells. Observation by transmission electron microscopy and flow cytometry further confirmed the cytotoxicity as apoptosis. Our results show that the HIV1-TAT domain is a useful tool for transporting a low molecular weight protein across the cell membrane in vitro. The PTD-Grb2-SH2 may be a novel agent for breast cancer therapy.

  10. Inhibition of Cellular Adhesion by Immunological Targeting of Osteopontin Neoepitopes Generated through Matrix Metalloproteinase and Thrombin Cleavage.

    Science.gov (United States)

    Jürets, Alexander; Le Bras, Marie; Staffler, Günther; Stein, Gesine; Leitner, Lukas; Neuhofer, Angelika; Tardelli, Matteo; Turkof, Edvin; Zeyda, Maximilian; Stulnig, Thomas M

    2016-01-01

    Osteopontin (OPN), a secreted protein involved in inflammatory processes and cancer, induces cell adhesion, migration, and activation of inflammatory pathways in various cell types. Cells bind OPN via integrins at a canonical RGD region in the full length form as well as to a contiguous cryptic site that some have shown is unmasked upon thrombin or matrix metalloproteinase cleavage. Thus, the adhesive capacity of osteopontin is enhanced by proteolytic cleavage that may occur in inflammatory conditions such as obesity, atherosclerosis, rheumatoid arthritis, tumor growth and metastasis. Our aim was to inhibit cellular adhesion to recombinant truncated proteins that correspond to the N-terminal cleavage products of thrombin- or matrix metalloproteinase-cleaved OPN in vitro. We specifically targeted the cryptic integrin binding site with monoclonal antibodies and antisera induced by peptide immunization of mice. HEK 293 cells adhered markedly stronger to truncated OPN proteins than to full length OPN. Without affecting cell binding to the full length form, the raised monoclonal antibodies specifically impeded cellular adhesion to the OPN fragments. Moreover, we show that the peptides used for immunization were able to induce antisera, which impeded adhesion either to all OPN forms, including the full-length form, or selectively to the corresponding truncated recombinant proteins. In conclusion, we developed immunological tools to selectively target functional properties of protease-cleaved OPN forms, which could find applications in treatment and prevention of various inflammatory diseases and cancers.

  11. Detection of siRNA Mediated Target mRNA Cleavage Activities in Human Cells by a Novel Stem-Loop Array RT-PCR Analysis

    Science.gov (United States)

    2016-09-07

    sequences of the target mRNA, and a double stranded stem at the 5′ end that forms a stem -loop to function as a forceps to stabilize the secondary...E-mjournal homepage: www.elsevier.com/locate/bbrepDetection of siRNA-mediated target mRNA cleavage activities in human cells by a novel stem -loop...challenges for the accurate and efficient detection and verification of cleavage sites on target mRNAs. Here we used a sensitive stem -loop array reverse

  12. Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, B; Dunlop, JI; Batten, MR

    2000-01-01

    , Streptococcus pneumoniae, S. sanguis, Neisseria meningitidis types 1 and 2, N. gonorrhoeae types 1 and 2, and Haemophilus influenzae type 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required, are provided...... by either an IgA1 or an IgA2 framework. In contrast, the IgA2/A1 hybrid appeared to be resistant to cleavage with S. oralis and some H. influenzae type 1 IgA1 proteases, suggesting these enzymes require additional determinants for efficient substrate recognition....

  13. Drosha regulates gene expression independently of RNA cleavage function

    DEFF Research Database (Denmark)

    Gromak, Natalia; Dienstbier, Martin; Macias, Sara

    2013-01-01

    Drosha is the main RNase III-like enzyme involved in the process of microRNA (miRNA) biogenesis in the nucleus. Using whole-genome ChIP-on-chip analysis, we demonstrate that, in addition to miRNA sequences, Drosha specifically binds promoter-proximal regions of many human genes in a transcription......-dependent manner. This binding is not associated with miRNA production or RNA cleavage. Drosha knockdown in HeLa cells downregulated nascent gene transcription, resulting in a reduction of polyadenylated mRNA produced from these gene regions. Furthermore, we show that this function of Drosha is dependent on its N......-terminal protein-interaction domain, which associates with the RNA-binding protein CBP80 and RNA Polymerase II. Consequently, we uncover a previously unsuspected RNA cleavage-independent function of Drosha in the regulation of human gene expression....

  14. Polycystin-1 Cleavage and the Regulation of Transcriptional Pathways

    Science.gov (United States)

    Merrick, David; Bertuccio, Claudia A.; Chapin, Hannah C.; Lal, Mark; Chauvet, Veronique; Caplan, Michael J.

    2013-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end stage renal disease, affecting ~1 in 1,000 people. The disease is characterized by the development of numerous large fluid filled renal cysts over the course of decades. These cysts compress the surrounding renal parenchyma and impair its function. Mutations in two genes are responsible for ADPKD. The protein products of both of these genes, polycystin-1 and polycystin-2, localize to the primary cilium and participate in a wide variety of signaling pathways. Polycystin-1 undergoes several proteolytic cleavages that produce fragments that manifest biological activities. Recent results suggest that the production of polycystin-1 cleavage fragments is necessary and sufficient to account for at least some, although certainly not all, of the physiological functions of the parent protein. PMID:23824180

  15. Cleavage of cohesin rings coordinates the separation of centrioles and chromatids.

    Science.gov (United States)

    Schöckel, Laura; Möckel, Martin; Mayer, Bernd; Boos, Dominik; Stemmann, Olaf

    2011-07-10

    Cohesin pairs sister chromatids by forming a tripartite Scc1-Smc1-Smc3 ring around them. In mitosis, cohesin is removed from chromosome arms by the phosphorylation-dependent prophase pathway. Centromeric cohesin is protected by shugoshin 1 and protein phosphatase 2A (Sgo1-PP2A) and opened only in anaphase by separase-dependent cleavage of Scc1 (refs 4-6). Following chromosome segregation, centrioles loosen their tight orthogonal arrangement, which licenses later centrosome duplication in S phase. Although a role of separase in centriole disengagement has been reported, the molecular details of this process remain enigmatic. Here, we identify cohesin as a centriole-engagement factor. Both premature sister-chromatid separation and centriole disengagement are induced by ectopic activation of separase or depletion of Sgo1. These unscheduled events are suppressed by expression of non-cleavable Scc1 or inhibition of the prophase pathway. When endogenous Scc1 is replaced by artificially cleavable Scc1, the corresponding site-specific protease triggers centriole disengagement. Separation of centrioles can alternatively be induced by ectopic cleavage of an engineered Smc3. Thus, the chromosome and centrosome cycles exhibit extensive parallels and are coordinated with each other by dual use of the cohesin ring complex.

  16. DISCOVERY OF THE BROAD-LINED TYPE Ic SN 2013cq ASSOCIATED WITH THE VERY ENERGETIC GRB 130427A

    Energy Technology Data Exchange (ETDEWEB)

    Xu, D.; Krühler, T.; Hjorth, J.; Malesani, D.; Fynbo, J. P. U.; Watson, D. J.; Geier, S. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 København Ø (Denmark); De Ugarte Postigo, A.; Thöne, C. C.; Sánchez-Ramírez, R. [Instituto de Astrofísica de Andalucía, CSIC, Glorieta de la Astronomía s/n, E-18008 Granada (Spain); Leloudas, G. [The Oskar Klein Centre, Department of Physics, Stockholm University, AlbaNova, SE-10691 Stockholm (Sweden); Cano, Z.; Jakobsson, P. [Centre for Astrophysics and Cosmology, Science Institute, University of Iceland, Dunhagi 5, IS-107 Reykjavik (Iceland); Schulze, S. [Departamento de Astronomía y Astrofísica, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 22 (Chile); Kaper, L. [Astronomical Institute Anton Pannekoek, University of Amsterdam, Science Park 904, NL-1098 XH Amsterdam (Netherlands); Sollerman, J. [The Oskar Klein Centre, Department of Astronomy, Stockholm University, AlbaNova, SE-10691 Stockholm (Sweden); Cabrera-Lavers, A. [Instituto de Astrofísica de Canarias, E-38205 La Laguna, Tenerife (Spain); Cao, C. [Department of Space Science and Physics, Shandong University at Weihai, Weihai, Shandong 264209 (China); Covino, S. [INAF/Brera Astronomical Observatory, via Bianchi 46, I-23807 Merate (Italy); Flores, H., E-mail: dong@dark-cosmology.dk [Laboratoire Galaxies Etoiles Physique et Instrumentation, Observatoire de Paris, 5 place Jules Janssen, F-92195 Meudon (France); and others

    2013-10-20

    Long-duration gamma-ray bursts (GRBs) at z < 1 are found in most cases to be accompanied by bright, broad-lined Type Ic supernovae (SNe Ic-BL). The highest-energy GRBs are mostly located at higher redshifts, where the associated SNe are hard to detect observationally. Here, we present early and late observations of the optical counterpart of the very energetic GRB 130427A. Despite its moderate redshift, z = 0.3399 ± 0.0002, GRB 130427A is at the high end of the GRB energy distribution, with an isotropic-equivalent energy release of E{sub iso} ∼ 9.6 × 10{sup 53} erg, more than an order of magnitude more energetic than other GRBs with spectroscopically confirmed SNe. In our dense photometric monitoring, we detect excess flux in the host-subtracted r-band light curve, consistent with that expected from an emerging SN, ∼0.2 mag fainter than the prototypical SN 1998bw. A spectrum obtained around the time of the SN peak (16.7 days after the GRB) reveals broad undulations typical of SNe Ic-BL, confirming the presence of an SN, designated SN 2013cq. The spectral shape and early peak time are similar to those of the high expansion velocity SN 2010bh associated with GRB 100316D. Our findings demonstrate that high-energy, long-duration GRBs, commonly detected at high redshift, can also be associated with SNe Ic-BL, pointing to a common progenitor mechanism.

  17. THE OPTICAL AFTERGLOW AND z = 0.92 EARLY-TYPE HOST GALAXY OF THE SHORT GRB 100117A

    International Nuclear Information System (INIS)

    Fong, W.; Berger, E.; Chornock, R.; Tanvir, N. R.; Levan, A. J.; Fruchter, A. S.; Graham, J. F.; Cucchiara, A.; Fox, D. B.

    2011-01-01

    We present the discovery of the optical afterglow and early-type host galaxy of the short-duration GRB 100117A. The faint afterglow is detected 8.3 hr after the burst with r AB = 25.46 ± 0.20 mag. Follow-up optical and near-infrared observations uncover a coincident compact red galaxy, identified as an early-type galaxy at a spectroscopic redshift of z ∼ 0.915 with a mass of ∼3 x 10 10 M sun , an age of ∼1 Gyr, and a luminosity of L B ≅ 0.5 L * . From a possible weak detection of [O II]λ3727 emission at z = 0.915 we infer an upper bound on the star formation rate of ∼0.1 M sun yr -1 , leading to a specific star formation rate of ∼ -1 . Thus, GRB 100117A is only the second short burst to date with a secure early-type host (the other being GRB 050724 at z = 0.257) and it has one of the highest short gamma-ray burst (GRB) redshifts. The offset between the host center and the burst position, 470 ± 310 pc, is the smallest to date. Combined with the old stellar population age, this indicates that the burst likely originated from a progenitor with no significant kick velocity. However, from the brightness of the optical afterglow we infer a relatively low density of n ∼ 3 x 10 -4 ε -3 e,-1 ε -1.75 B,-1 cm -3 . The combination of an optically faint afterglow and host suggests that previous such events may have been missed, thereby potentially biasing the known short GRB host population against z ∼> 1 early-type hosts.

  18. SEARCH FOR GAMMA-RAYS FROM THE UNUSUALLY BRIGHT GRB 130427A WITH THE HAWC GAMMA-RAY OBSERVATORY

    Energy Technology Data Exchange (ETDEWEB)

    Abeysekara, A. U. [Department of Physics and Astronomy, Michigan State University, East Lansing, MI (United States); Alfaro, R. [Instituto de Física, Universidad Nacional Autónoma de México, México D. F. (Mexico); Alvarez, C.; Arceo, R. [CEFyMAP, Universidad Autónoma de Chiapas, Tuxtla Gutiérrez, Chiapas (Mexico); Álvarez, J. D.; Arteaga-Velázquez, J. C.; Cotti, U.; De León, C. [Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán (Mexico); Solares, H. A. Ayala [Department of Physics, Michigan Technological University, Houghton, MI (United States); Barber, A. S. [Department of Physics and Astronomy, University of Utah, Salt Lake City, UT (United States); Baughman, B. M.; Braun, J. [Department of Physics, University of Maryland, College Park, MD (United States); Bautista-Elivar, N. [Universidad Politécnica de Pachuca, Municipio de Zempoala, Hidalgo (Mexico); BenZvi, S. Y. [Department of Physics and Astronomy, University of Rochester, Rochester, NY (United States); Rosales, M. Bonilla; Carramiñana, A. [Instituto Nacional de Astrofísica, Óptica y Electrónica, Tonantzintla, Puebla (Mexico); Caballero-Mora, K. S. [Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México D. F. (Mexico); Castillo, M.; Cotzomi, J. [Facultad de Ciencias Físico Matemáticas, Benemérita Universidad Autónoma de Puebla, Ciudad Universitaria, Puebla (Mexico); De la Fuente, E., E-mail: dirk.lennarz@gatech.edu [Departamento de Física, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara (Mexico); Collaboration: HAWC collaboration; and others

    2015-02-20

    The first limits on the prompt emission from the long gamma-ray burst (GRB) 130427A in the >100 GeV energy band are reported. GRB 130427A was the most powerful burst ever detected with a redshift z ≲ 0.5 and featured the longest lasting emission above 100 MeV. The energy spectrum extends at least up to 95 GeV, clearly in the range observable by the High Altitude Water Cherenkov (HAWC) Gamma-Ray Observatory, a new extensive air shower detector currently under construction in central Mexico. The burst occurred under unfavorable observation conditions, low in the sky and when HAWC was running 10% of the final detector. Based on the observed light curve at MeV-GeV energies, eight different time periods have been searched for prompt and delayed emission from this GRB. In all cases, no statistically significant excess of counts has been found and upper limits have been placed. It is shown that a similar GRB close to zenith would be easily detected by the full HAWC detector, which will be completed soon. The detection rate of the full HAWC detector may be as high as one to two GRBs per year. A detection could provide important information regarding the high energy processes at work and the observation of a possible cut-off beyond the Fermi Large Area Telescope energy range could be the signature of gamma-ray absorption, either in the GRB or along the line of sight due to the extragalactic background light.

  19. Hubble space telescope observations of the afterglow, supernova, and host galaxy associated with the extremely bright GRB 130427A

    Energy Technology Data Exchange (ETDEWEB)

    Levan, A. J. [Department of Physics, University of Warwick, Coventry, CV4 7AL (United Kingdom); Tanvir, N. R.; Wiersema, K. [Department of Physics and Astronomy, University of Leicester, University Road, Leicester, LE1 7RH (United Kingdom); Fruchter, A. S.; Hounsell, R. A.; Graham, J. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Hjorth, J.; Fynbo, J. P. U. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark); Pian, E. [INAF, Trieste Astronomical Observatory, via G.B. Tiepolo 11, I-34143 Trieste (Italy); Mazzali, P. [Astrophysics Research Institute, Liverpool John Moores University, IC2 Liverpool Science Park 146 Brownlow Hill, Liverpool L3 5RF (United Kingdom); Perley, D. A. [Department of Astronomy, California Institute of Technology, MC 249-17, 1200 East California Blvd., Pasadena, CA 91125 (United States); Cano, Z. [Centre for Astrophysics and Cosmology, Science Institute, University of Iceland, Dunhagi 5, 107 Reykjavik (Iceland); Cenko, S. B. [Astrophysics Science Division, NASA Goddard Space Flight Center, Mail Code 661, Greenbelt, MD 20771 (United States); Kouveliotou, C. [Science and Technology Office, ZP12, NASA/Marshall Space Flight Center, Huntsville, AL 35812 (United States); Pe' er, A. [Department of Physics, University College Cork, Cork (Ireland); Misra, K., E-mail: a.j.levan@warwick.ac.uk [Aryabhatta Research Institute of Observational Sciences, Manora Peak, Nainital-263 002 (India)

    2014-09-10

    We present Hubble Space Telescope (HST) observations of the exceptionally bright and luminous Swift gamma-ray burst (GRB), GRB 130427A. At z = 0.34, this burst affords an excellent opportunity to study the supernova (SN) and host galaxy associated with an intrinsically extremely luminous burst (E {sub iso} > 10{sup 54} erg): more luminous than any previous GRB with a spectroscopically associated SN. We use the combination of the image quality, UV capability, and invariant point-spread function of HST to provide the best possible separation of the afterglow, host, and SN contributions to the observed light ∼17 rest-frame days after the burst, utilizing a host subtraction spectrum obtained one year later. Advanced Camera for Surveys grism observations show that the associated SN, SN 2013cq, has an overall spectral shape and luminosity similar to SN 1998bw (with a photospheric velocity, v {sub ph} ∼ 15, 000 km s{sup –1}). The positions of the bluer features are better matched by the higher velocity SN 2010bh (v {sub ph} ∼ 30, 000 km s{sup –1}), but this SN is significantly fainter and fails to reproduce the overall spectral shape, perhaps indicative of velocity structure in the ejecta. We find that the burst originated ∼4 kpc from the nucleus of a moderately star forming (1 M {sub ☉} yr{sup –1}), possibly interacting disk galaxy. The absolute magnitude, physical size, and morphology of this galaxy, as well as the location of the GRB within it, are also strikingly similar to those of GRB 980425/SN 1998bw. The similarity of the SNe and environment from both the most luminous and least luminous GRBs suggests that broadly similar progenitor stars can create GRBs across six orders of magnitude in isotropic energy.

  20. DISCOVERY AND REDSHIFT OF AN OPTICAL AFTERGLOW IN 71 deg2: iPTF13bxl AND GRB 130702A

    International Nuclear Information System (INIS)

    Singer, Leo P.; Brown, Duncan A.; Bradley Cenko, S.; Gehrels, Neil; McEnery, Julie; Kasliwal, Mansi M.; Mulchaey, John; Perley, Daniel A.; Kulkarni, S. R.; Bellm, Eric; Barlow, Tom; Cao, Yi; Horesh, Assaf; Ofek, Eran O.; Arcavi, Iair; Nugent, Peter E.; Bloom, Joshua S.; Corsi, Alessandra; Frail, Dale A.; Masci, Frank J.

    2013-01-01

    We report the discovery of the optical afterglow of the γ-ray burst (GRB) 130702A, identified upon searching 71 deg 2 surrounding the Fermi Gamma-ray Burst Monitor (GBM) localization. Discovered and characterized by the intermediate Palomar Transient Factory, iPTF13bxl is the first afterglow discovered solely based on a GBM localization. Real-time image subtraction, machine learning, human vetting, and rapid response multi-wavelength follow-up enabled us to quickly narrow a list of 27,004 optical transient candidates to a single afterglow-like source. Detection of a new, fading X-ray source by Swift and a radio counterpart by CARMA and the Very Large Array confirmed the association between iPTF13bxl and GRB 130702A. Spectroscopy with the Magellan and Palomar 200 inch telescopes showed the afterglow to be at a redshift of z = 0.145, placing GRB 130702A among the lowest redshift GRBs detected to date. The prompt γ-ray energy release and afterglow luminosity are intermediate between typical cosmological GRBs and nearby sub-luminous events such as GRB 980425 and GRB 060218. The bright afterglow and emerging supernova offer an opportunity for extensive panchromatic follow-up. Our discovery of iPTF13bxl demonstrates the first observational proof-of-principle for ∼10 Fermi-iPTF localizations annually. Furthermore, it represents an important step toward overcoming the challenges inherent in uncovering faint optical counterparts to comparably localized gravitational wave events in the Advanced LIGO and Virgo era

  1. Relationship between synthesis and cleavage of poliovirus-specific proteins.

    OpenAIRE

    Thomas, A A; Voorma, H O; Boeye, A

    1983-01-01

    Poliovirus proteinase was studied in vitro in lysates from poliovirus-infected HeLa cells. Preincubation of these lysates caused (i) a reduction in poliovirus proteinase activity and (ii) a partial dependence on exogenous mRNA for optimal translation. Proteins translated from endogenous poliovirus RNA in preincubated extracts from virus-infected HeLa cells are poorly cleaved. This cleavage deficiency is alleviated by adding fresh poliovirus RNA to the translation system, thus, allowing re-ini...

  2. Effects of Cysteamine on Sheep Embryo Cleavage Rates

    Directory of Open Access Journals (Sweden)

    Sinem Ö. ENGİNLER

    2015-01-01

    Full Text Available Oxidative stress during in vitro culture leads to defects in development of gametes and embryos. Several antioxidants such as cysteamine, L-ascorbic acid, beta mercaptoethanol, cysteine, glutathione, proteins, vitamins have been used to supplement culture media to counter the oxidative stress. This study was conducted to detect the effect of adding cysteamine to the maturation medium to subsequent cleavage rates of sheep embryos. Totally 604 ovaries were obtained by ten replica and 2060 oocytes were collected. The cumulus oocyte complexes were recovered by the slicing method. A total of 1818 selected oocytes were divided into two groups and used for maturation (88.25%. The first group was created as supplemented with cysteamine (Group A and second group (Group B, control without cysteamine in TCM-199. The two groups were incubated for 24 h at 38.8 °C in an atmosphere of 5% CO2 in humidified air for in vitro maturation (IVM. After IVM, oocytes were fertilized with 50 x 107 / mL fresh ram semen in BSOF medium for 18 h. After fertilization, maturation groups were divided into two subgroups with different culture media: Group AI-SOF (Synthetic Oviduct Fluid medium, Group AII-CR1aa (Charles Rosencrans medium, Group BI-SOF and Group BII-CR1aa were achieved. Cleavage rates were evaluated at day 2. post insemination. The rates of cleavage were detected as 59.54% (184/309, 55.44% (173/312, 65.34% (215/329, 59.34% (200/337 respectively, with showing no statistically significant difference between the groups at the level of P>0.05. In conclusion, supplementing cysteamine to maturation media in TCM-199 did not affect the cleavage rates of sheep embryos in SOF and CR1aa culture media.

  3. Deletion of the thrombin cleavage domain of osteopontin mediates breast cancer cell adhesion, proteolytic activity, tumorgenicity, and metastasis

    International Nuclear Information System (INIS)

    Beausoleil, Michel S; Schulze, Erika B; Goodale, David; Postenka, Carl O; Allan, Alison L

    2011-01-01

    Osteopontin (OPN) is a secreted phosphoprotein often overexpressed at high levels in the blood and primary tumors of breast cancer patients. OPN contains two integrin-binding sites and a thrombin cleavage domain located in close proximity to each other. To study the role of the thrombin cleavage site of OPN, MDA-MB-468 human breast cancer cells were stably transfected with either wildtype OPN (468-OPN), mutant OPN lacking the thrombin cleavage domain (468-ΔTC) or an empty vector (468-CON) and assessed for in vitro and in vivo functional differences in malignant/metastatic behavior. All three cell lines were found to equivalently express thrombin, tissue factor, CD44, αvβ5 integrin and β1 integrin. Relative to 468-OPN and 468-CON cells, 468-ΔTC cells expressing OPN with a deleted thrombin cleavage domain demonstrated decreased cell adhesion (p < 0.001), decreased mRNA expression of MCAM, maspin and TRAIL (p < 0.01), and increased uPA expression and activity (p < 0.01) in vitro. Furthermore, injection of 468-ΔTC cells into the mammary fat pad of nude mice resulted in decreased primary tumor latency time (p < 0.01) and increased primary tumor growth and lymph node metastatic burden (p < 0.001) compared to 468-OPN and 468-CON cells. The results presented here suggest that expression of thrombin-uncleavable OPN imparts an early tumor formation advantage as well as a metastatic advantage for breast cancer cells, possibly due to increased proteolytic activity and decreased adhesion and apoptosis. Clarification of the mechanisms responsible for these observations and the translation of this knowledge into the clinic could ultimately provide new therapeutic opportunities for combating breast cancer

  4. Numerical modeling of ductile tearing effects on cleavage fracture toughness

    International Nuclear Information System (INIS)

    Dodds, R.H. Jr.; Tang, M.; Anderson, T.L.

    1994-05-01

    Experimental studies demonstrate a significant effect of specimen size, a/W ratio and prior ductile tearing on cleavage fracture toughness values (J c ) measured in the ductile-to-brittle transition region of ferritic materials. In the lower-transition region, cleavage fracture often occurs under conditions of large-scale yielding but without prior ductile crack extension. The increased toughness develops when plastic zones formed at the crack tip interact with nearby specimen surfaces which relaxes crack-tip constraint (stress triaxiality). In the mid-to-upper transition region, small amounts of ductile crack extension (often c -values. Previous work by the authors described a micromechanics fracture model to correct measured J c -values for the mechanistic effects of large-scale yielding. This new work extends the model to also include the influence of ductile crack extension prior to cleavage. The paper explores development of the new model, provides necessary graphs and procedures for its application and demonstrates the effects of the model on fracture data sets for two pressure vessel steels (A533B and A515)

  5. Cleavage mechanoluminescence in elemental and III-V semiconductors

    International Nuclear Information System (INIS)

    Chandra, B.P.; Patel, R.P.; Gour, Anubha S.; Chandra, V.K.; Gupta, R.K.

    2003-01-01

    The present paper reports the theory of mechanoluminescence (ML) produced during cleavage of elemental and III-V semiconductors. It seems that the formation of crack-induced localized states is responsible for the ML excitation produced during the cleavage of elemental and III-V semiconductors. According to this mechanism, as the atoms are drawn away from each other in an advancing crack tip, the decreasing wave function overlap across the crack may result in localized states which is associated with increasing electron energy. If the energy of these localized states approach that of the conduction band, transition to the conduction band via tunnelling would be possible, creating minority carriers, and consequently the electron-hole recombination may give rise to mechanoluminescence. When an elemental or III-V semiconductor is cleaved, initially the ML intensity increases with time, attains a peak value I m at the time t m corresponding to completion of the cleavage of the semiconductor, and then it decreases following power law decay. Expressions are derived for the ML intensity I m corresponding to the peak of the ML intensity versus time curve and for the total ML intensity I T . It is shown that both I m and I T should increase directly with the area of the newly created surfaces of the crystals. From the measurements of the ML intensity, the velocity of crack propagation in material can be determined by using the relation v=H/t m

  6. Specific in vitro cleavage of Mason-Pfizer monkey virus capsid protein: evidence for a potential role of retroviral protease in early stages of infection

    International Nuclear Information System (INIS)

    Rumlova, Michaela; Ruml, Tomas; Pohl, Jan; Pichova, Iva

    2003-01-01

    Processing of Gag polyproteins by viral protease (PR) leads to reorganization of immature retroviral particles and formation of a ribonucleoprotein core. In some retroviruses, such as HIV and RSV, cleavage of a spacer peptide separating capsid and nucleocapsid proteins is essential for the core formation. We show here that no similar spacer peptide is present in the capsid-nucleocapsid (CA-NC) region of Mason-Pfizer monkey virus (M-PMV) and that the CA protein is cleaved in vitro by the PR within the major homology region (MHR) and the NC protein in several sites at the N-terminus. The CA cleavage product was also identified shortly after penetration of M-PMV into COS cells, suggesting that the protease-catalyzed cleavage is involved in core disintegration

  7. Sequence adaptations affecting cleavage of the VP1/2A junction by the 3C protease in foot-and-mouth disease virus-infected cells

    DEFF Research Database (Denmark)

    Gullberg, Maria; Polacek, Charlotta; Belsham, Graham

    2014-01-01

    The foot-and-mouth disease virus (FMDV) capsid protein precursor P1-2A is cleaved by the virus-encoded 3C protease to VP0, VP3, VP1 and 2A. It was shown previously that modification of a single amino acid residue (K210E) within the VP1 protein and close to the VP1/2A cleavage site, inhibited...... cleavage of this junction and produced 'self-tagged' virus particles. A second site substitution (E83K) within VP1 was also observed within the rescued virus [Gullberg et al. (2013). J Virol 87: , 11591-11603]. It was shown here that introduction of this E83K change alone into a serotype O virus resulted...... in the rapid accumulation of a second site substitution within the 2A sequence (L2P), which also blocked VP1/2A cleavage. This suggests a linkage between the E83K change in VP1 and cleavage of the VP1/2A junction. Cells infected with viruses containing the VP1 K210E or the 2A L2P substitutions contained...

  8. [Recent knowledge about intestinal absorption and cleavage of carotenoids].

    Science.gov (United States)

    Borel, P; Drai, J; Faure, H; Fayol, V; Galabert, C; Laromiguière, M; Le Moël, G

    2005-01-01

    Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the

  9. GRB 100816

    DEFF Research Database (Denmark)

    Malesani, Daniele; Xu, Dong; Fynbo, Johan Peter Uldall

    2011-01-01

    ) and the putative host galaxy (Im et al., GCN 11108; Tanvir et al., GCN 11109). We find magnitudes of R = 23.0 +- 0.1 and R = 21.65 +- 0.05 for the two objects, respectively, assuming R=17.06 for the nearby USNO star 1165-0595190. We caution that accurate photometry will have to await for late-time templates...

  10. The host galaxy and optical light curve of the gamma-ray burst GRB 980703

    DEFF Research Database (Denmark)

    Holland, S.; Fynbo, J.P.U.; Hjorth, J.

    2001-01-01

    We present deep HST/STIS and ground-based photometry of the host galaxy of the gamma-ray burst GRB 980703 taken 17, 551, 710, and 716 days after the burst. We find that the host is a blue, slightly over-luminous galaxy with V-gal = 23.00 +/-0.10, (V - R)(gal) = 0.43 +/-0.13, and a centre...... 980703 with any special features in the host. The host galaxy appears to be a typical example of a compact star forming galaxy similar to those found in the Hubble Deep Field North. The R-band light curve of the optical afterglow associated with this gamma-ray burst is consistent with a single power...

  11. Broadband observations of the naked-eye gamma-ray burst GRB 080319B.

    Science.gov (United States)

    Racusin, J L; Karpov, S V; Sokolowski, M; Granot, J; Wu, X F; Pal'shin, V; Covino, S; van der Horst, A J; Oates, S R; Schady, P; Smith, R J; Cummings, J; Starling, R L C; Piotrowski, L W; Zhang, B; Evans, P A; Holland, S T; Malek, K; Page, M T; Vetere, L; Margutti, R; Guidorzi, C; Kamble, A P; Curran, P A; Beardmore, A; Kouveliotou, C; Mankiewicz, L; Melandri, A; O'Brien, P T; Page, K L; Piran, T; Tanvir, N R; Wrochna, G; Aptekar, R L; Barthelmy, S; Bartolini, C; Beskin, G M; Bondar, S; Bremer, M; Campana, S; Castro-Tirado, A; Cucchiara, A; Cwiok, M; D'Avanzo, P; D'Elia, V; Valle, M Della; de Ugarte Postigo, A; Dominik, W; Falcone, A; Fiore, F; Fox, D B; Frederiks, D D; Fruchter, A S; Fugazza, D; Garrett, M A; Gehrels, N; Golenetskii, S; Gomboc, A; Gorosabel, J; Greco, G; Guarnieri, A; Immler, S; Jelinek, M; Kasprowicz, G; La Parola, V; Levan, A J; Mangano, V; Mazets, E P; Molinari, E; Moretti, A; Nawrocki, K; Oleynik, P P; Osborne, J P; Pagani, C; Pandey, S B; Paragi, Z; Perri, M; Piccioni, A; Ramirez-Ruiz, E; Roming, P W A; Steele, I A; Strom, R G; Testa, V; Tosti, G; Ulanov, M V; Wiersema, K; Wijers, R A M J; Winters, J M; Zarnecki, A F; Zerbi, F; Mészáros, P; Chincarini, G; Burrows, D N

    2008-09-11

    Long-duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of massive stars. Previous early optical observations of even the most exceptional GRBs (990123 and 030329) lacked both the temporal resolution to probe the optical flash in detail and the accuracy needed to trace the transition from the prompt emission within the outflow to external shocks caused by interaction with the progenitor environment. Here we report observations of the extraordinarily bright prompt optical and gamma-ray emission of GRB 080319B that provide diagnostics within seconds of its formation, followed by broadband observations of the afterglow decay that continued for weeks. We show that the prompt emission stems from a single physical region, implying an extremely relativistic outflow that propagates within the narrow inner core of a two-component jet.

  12. THE AFTERGLOW AND ULIRG HOST GALAXY OF THE DARK SHORT GRB 120804A

    Energy Technology Data Exchange (ETDEWEB)

    Berger, E.; Zauderer, B. A.; Margutti, R.; Laskar, T.; Fong, W.; Chornock, R.; Dupuy, T. J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Levan, A.; Tunnicliffe, R. L. [Department of Physics, University of Warwick, Coventry CV4 7AL (United Kingdom); Mangano, V. [INAF, Istituto di Astrofisica Spaziale e Fisica Cosmica, Via U. La Malfa 153, I-90146 Palermo (Italy); Fox, D. B. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Tanvir, N. R. [Department of Physics and Astronomy, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Menten, K. M. [Max-Planck-Institut fuer Radioastronomie, Auf dem Huegel 69, D-53121 Bonn (Germany); Hjorth, J. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen O (Denmark); Roth, K. [Gemini Observatory, 670 North Aohoku Place, Hilo, HI 96720 (United States)

    2013-03-10

    We present the optical discovery and subarcsecond optical and X-ray localization of the afterglow of the short GRB 120804A, as well as optical, near-IR, and radio detections of its host galaxy. X-ray observations with Swift/XRT, Chandra, and XMM-Newton extending to {delta}t Almost-Equal-To 19 days reveal a single power-law decline. The optical afterglow is faint, and comparison to the X-ray flux indicates that GRB 120804A is ''dark'', with a rest-frame extinction of A {sup host}{sub V} Almost-Equal-To 2.5 mag (at z = 1.3). The intrinsic neutral hydrogen column density inferred from the X-ray spectrum, N{sub H,{sub int}}(z = 1.3) Almost-Equal-To 2 Multiplication-Sign 10{sup 22} cm{sup -2}, is commensurate with the large extinction. The host galaxy exhibits red optical/near-IR colors. Equally important, JVLA observations at Almost-Equal-To 0.9-11 days reveal a constant flux density of F{sub {nu}}(5.8 GHz) = 35 {+-} 4 {mu}Jy and an optically thin spectrum, unprecedented for GRB afterglows, but suggestive instead of emission from the host galaxy. The optical/near-IR and radio fluxes are well fit with the scaled spectral energy distribution of the local ultraluminous infrared galaxy (ULIRG) Arp 220 at z Almost-Equal-To 1.3, with a resulting star formation rate of x Almost-Equal-To 300 M{sub Sun} yr{sup -1}. The inferred extinction and small projected offset (2.2 {+-} 1.2 kpc) are also consistent with the ULIRG scenario, as is the presence of a companion galaxy at the same redshift and with a separation of about 11 kpc. The limits on radio afterglow emission, in conjunction with the observed X-ray and optical emission, require a circumburst density of n {approx} 10{sup -3} cm{sup -3}, an isotropic-equivalent energy scale of E{sub {gamma},{sub iso}} Almost-Equal-To E{sub K,{sub iso}} Almost-Equal-To 7 Multiplication-Sign 10{sup 51} erg, and a jet opening angle of {theta}{sub j} {approx}> 11 Degree-Sign . The expected fraction of luminous infrared

  13. OBSERVATIONAL SEARCH FOR PeV-EeV TAU NEUTRINO FROM GRB081203A

    International Nuclear Information System (INIS)

    Aita, Y.; Aoki, T.; Asaoka, Y.; Chonan, T.; Jobashi, M.; Masuda, M.; Morimoto, Y.; Noda, K.; Sasaki, M.; Asoh, J.; Ishikawa, N.; Ogawa, S.; Learned, J. G.; Matsuno, S.; Olsen, S.; Binder, P.-M.; Hamilton, J.; Sugiyama, N.; Watanabe, Y.

    2011-01-01

    We report the first observational search for tau neutrinos (ν τ ) from gamma-ray bursts (GRBs) using one of the Ashra light collectors. The Earth-skimming ν τ technique of imaging Cherenkov τ showers was applied as a detection method. We set stringent upper limits on the ν τ fluence in PeV-EeV region for 3780 s (between 2.83 and 1.78 hr before) and another 3780 s (between 21.2 and 22.2 hr after) surrounding GRB081203A triggered by the Swift satellite. This first search for PeV-EeV ν τ complements other experiments in energy range and methodology, and suggests the prologue of 'multi-particle astronomy' with a precise determination of time and location.

  14. Microbiologically influenced corrosion of sa106 gr.b carbon steel in raw water

    International Nuclear Information System (INIS)

    Tunaru, M.; Velciu, L.; Stancu, M.; Popa, L.

    2015-01-01

    This paper presents the evaluation of microbiological corrosion susceptibility of carbon steel SA106gr.B in raw water. The experiment consisted of a series of electrochemical accelerated tests which evaluated the pitting corrosion susceptibility and determined corrosion rates before and after the immersion. The microbiological analysis of the water determined the types of bacteria and bacterial concentration present in water and in biofilms. Microbiological analysis of the water sample emphasized the existence, in small numbers (10-101 ml-1), of heterotrophic aerobic bacteria, sulphate-reducing bacteria and iron-oxidizing microorganisms. Along with sulphate-reducing bacteria, the heterotrophic aerobic bacteria and the iron-oxidizing microorganisms are categorized as having an important role in the corrosion of metals, including steel. The surfaces of the tested samples were analysed using the optical and electronic microscope, and emphasized the role of bacteria in the development of biofilms under which appeared characteristics of corrosion attack. (authors)

  15. Observation of X-ray lines from a gamma-ray burst (GRB991216): evidence of moving ejecta from the progenitor.

    Science.gov (United States)

    Piro, L; Garmire, G; Garcia, M; Stratta, G; Costa, E; Feroci, M; Mészáros, P; Vietri, M; Bradt, H; Frail, D; Frontera, F; Halpern, J; Heise, J; Hurley, K; Kawai, N; Kippen, R M; Marshall, F; Murakami, T; Sokolov, V V; Takeshima, T; Yoshida, A

    2000-11-03

    We report on the discovery of two emission features observed in the x-ray spectrum of the afterglow of the gamma-ray burst (GRB) of 16 December 1999 by the Chandra X-ray Observatory. These features are identified with the Ly(alpha) line and the narrow recombination continuum by hydrogenic ions of iron at a redshift z = 1.00 +/- 0.02, providing an unambiguous measurement of the distance of a GRB. Line width and intensity imply that the progenitor of the GRB was a massive star system that ejected, before the GRB event, a quantity of iron approximately 0.01 of the mass of the sun at a velocity approximately 0.1 of the speed of light, probably by a supernova explosion.

  16. Significant and variable linear polarization during the prompt optical flash of GRB 160625B.

    Science.gov (United States)

    Troja, E.; Lipunov, V. M.; Mundell, C. G.; Butler, N. R.; Watson, A. M.; Kobayashi, S.; Cenko, S. B.; Marshall, F. E.; Ricci, R.; Fruchter, A.; Wieringa, M. H.; Gorbovskoy, E. S.; Kornilov, V.; Kutyrev, A.; Lee, W. H.; Toy, V.; Tyurina, N. V.; Budnev, N. M.; Buckley, D. A. H.; González, J.; Gress, O.; Horesh, A.; Panasyuk, M. I.; Prochaska, J. X.; Ramirez-Ruiz, E.; Rebolo Lopez, R.; Richer, M. G.; Roman-Zuniga, C.; Serra-Ricart, M.; Yurkov, V.; Gehrels, N.

    2017-07-01

    Newly formed black holes of stellar mass launch collimated outflows (jets) of ionized matter that approach the speed of light. These outflows power prompt, brief and intense flashes of γ-rays known as γ-ray bursts (GRBs), followed by longer-lived afterglow radiation that is detected across the electromagnetic spectrum. Measuring the polarization of the observed GRB radiation provides a direct probe of the magnetic fields in the collimated jets. Rapid-response polarimetric observations of newly discovered bursts have probed the initial afterglow phase, and show that, minutes after the prompt emission has ended, the degree of linear polarization can be as high as 30 per cent - consistent with the idea that a stable, globally ordered magnetic field permeates the jet at large distances from the central source. By contrast, optical and γ-ray observations during the prompt phase have led to discordant and often controversial results, and no definitive conclusions have been reached regarding the origin of the prompt radiation or the configuration of the magnetic field. Here we report the detection of substantial (8.3 ± 0.8 per cent from our most conservative simulation), variable linear polarization of a prompt optical flash that accompanied the extremely energetic and long-lived prompt γ-ray emission from GRB 160625B. Our measurements probe the structure of the magnetic field at an early stage of the jet, closer to its central black hole, and show that the prompt phase is produced via fast-cooling synchrotron radiation in a large-scale magnetic field that is advected from the black hole and distorted by dissipation processes within the jet.

  17. PROPAGATION OF RELATIVISTIC, HYDRODYNAMIC, INTERMITTENT JETS IN A ROTATING, COLLAPSING GRB PROGENITOR STAR

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Jin-Jun [School of Astronomy and Space Science, Nanjing University, Nanjing 210046 (China); Zhang, Bing [Department of Physics and Astronomy, University of Nevada Las Vegas, NV 89154 (United States); Kuiper, Rolf, E-mail: gengjinjun@gmail.com, E-mail: zhang@physics.unlv.edu [Institute of Astronomy and Astrophysics, University of Tübingen, Auf der Morgenstelle 10, D-72076 Tübingen (Germany)

    2016-12-10

    The prompt emission of gamma-ray bursts (GRBs) is characterized by rapid variabilities, which may be a direct reflection of the unsteady central engine. We perform a series of axisymmetric 2.5-dimensional simulations to study the propagation of relativistic, hydrodynamic, intermittent jets through the envelope of a GRB progenitor star. A realistic rapidly rotating star is incorporated as the background of jet propagation, and the star is allowed to collapse due to the gravity of the central black hole. By modeling the intermittent jets with constant-luminosity pulses with equal on and off durations, we investigate how the half period, T , affects the jet dynamics. For relatively small T values (e.g., 0.2 s), the jet breakout time t {sub bo} depends on the opening angle of the jet, with narrower jets more penetrating and reaching the surface at shorter times. For T  ≤ 1 s, the reverse shock (RS) crosses each pulse before the jet penetrates through the stellar envelope. As a result, after the breakout of the first group of pulses at t {sub bo}, several subsequent pulses vanish before penetrating the star, causing a quiescent gap. For larger half periods ( T = 2.0 and 4.0 s), all the pulses can successfully penetrate through the envelope, since each pulse can propagate through the star before the RS crosses the shell. Our results may interpret the existence of a weak precursor in some long GRBs, given that the GRB central engine injects intermittent pulses with a half period T  ≤ 1 s. The observational data seem to be consistent with such a possibility.

  18. Synchrotron self-inverse Compton radiation from reverse shock on GRB 120326A

    Energy Technology Data Exchange (ETDEWEB)

    Urata, Yuji [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Huang, Kuiyun; Takahashi, Satoko [Academia Sinica Institute of Astronomy and Astrophysics, Taipei 106, Taiwan (China); Im, Myungshin; Kim, Jae-Woo; Jang, Minsung [Center for the Exploration of the Origin of the Universe, Department of Physics and Astronomy, FPRD, Seoul National University, Shillim-dong, San 56-1, Kwanak-gu, Seoul (Korea, Republic of); Yamaoka, Kazutaka [Solar-Terrestrial Environment Laboratory, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601 (Japan); Tashiro, Makoto [Department of Physics, Saitama University, Shimo-Okubo, Saitama 338-8570 (Japan); Pak, Soojong, E-mail: urata@astro.ncu.edu.tw [School of Space Research, Kyung Hee University, Yongin, Gyeonggi 446-701 (Korea, Republic of)

    2014-07-10

    We present multi-wavelength observations of a typical long duration GRB 120326A at z = 1.798, including rapid observations using a Submillimeter Array (SMA) and a comprehensive monitoring in the X-ray and optical. The SMA observation provided the fastest detection to date among seven submillimeter afterglows at 230 GHz. The prompt spectral analysis, using Swift and Suzaku, yielded a spectral peak energy of E{sub peak}{sup src}=107.8{sub −15.3}{sup +15.3} keV and an equivalent isotropic energy of E{sub iso} as 3.18{sub −0.32}{sup +0.40}×10{sup 52} erg. The temporal evolution and spectral properties in the optical were consistent with the standard forward shock synchrotron with jet collimation (6.°69 ± 0.°16). The forward shock modeling, using a two-dimensional relativistic hydrodynamic jet simulation, was also determined by the reasonable burst explosion and the synchrotron radiation parameters for the optical afterglow. The X-ray light curve showed no apparent jet break and the temporal decay index relation between the X-ray and optical (αo – α{sub X} = –1.45 ± 0.10) indicated different radiation processes in each of them. Introducing synchrotron self-inverse Compton radiation from reverse shock is a possible solution, and the detection and slow decay of the afterglow in submillimeter supports that this is a plausible idea. The observed temporal evolution and spectral properties, as well as forward shock modeling parameters, enabled us to determine reasonable functions to describe the afterglow properties. Because half of the events share similar properties in the X-ray and optical as the current event, GRB 120326A will be a benchmark with further rapid follow-ups, using submillimeter instruments such as an SMA and the Atacama Large Millimeter/submillimeter Array.

  19. Synchrotron self-inverse Compton radiation from reverse shock on GRB 120326A

    International Nuclear Information System (INIS)

    Urata, Yuji; Huang, Kuiyun; Takahashi, Satoko; Im, Myungshin; Kim, Jae-Woo; Jang, Minsung; Yamaoka, Kazutaka; Tashiro, Makoto; Pak, Soojong

    2014-01-01

    We present multi-wavelength observations of a typical long duration GRB 120326A at z = 1.798, including rapid observations using a Submillimeter Array (SMA) and a comprehensive monitoring in the X-ray and optical. The SMA observation provided the fastest detection to date among seven submillimeter afterglows at 230 GHz. The prompt spectral analysis, using Swift and Suzaku, yielded a spectral peak energy of E peak src =107.8 −15.3 +15.3 keV and an equivalent isotropic energy of E iso as 3.18 −0.32 +0.40 ×10 52 erg. The temporal evolution and spectral properties in the optical were consistent with the standard forward shock synchrotron with jet collimation (6.°69 ± 0.°16). The forward shock modeling, using a two-dimensional relativistic hydrodynamic jet simulation, was also determined by the reasonable burst explosion and the synchrotron radiation parameters for the optical afterglow. The X-ray light curve showed no apparent jet break and the temporal decay index relation between the X-ray and optical (αo – α X = –1.45 ± 0.10) indicated different radiation processes in each of them. Introducing synchrotron self-inverse Compton radiation from reverse shock is a possible solution, and the detection and slow decay of the afterglow in submillimeter supports that this is a plausible idea. The observed temporal evolution and spectral properties, as well as forward shock modeling parameters, enabled us to determine reasonable functions to describe the afterglow properties. Because half of the events share similar properties in the X-ray and optical as the current event, GRB 120326A will be a benchmark with further rapid follow-ups, using submillimeter instruments such as an SMA and the Atacama Large Millimeter/submillimeter Array.

  20. Steep extinction towards GRB 140506A reconciled from host galaxy observations: Evidence that steep reddening laws are local

    Science.gov (United States)

    Heintz, K. E.; Fynbo, J. P. U.; Jakobsson, P.; Krühler, T.; Christensen, L.; Watson, D.; Ledoux, C.; Noterdaeme, P.; Perley, D. A.; Rhodin, H.; Selsing, J.; Schulze, S.; Tanvir, N. R.; Møller, P.; Goldoni, P.; Xu, D.; Milvang-Jensen, B.

    2017-05-01

    We present the spectroscopic and photometric late-time follow-up of the host galaxy of the long-duration Swift γ-ray burst GRB 140506A at z = 0.889. The optical and near-infrared afterglow of this GRB had a peculiar spectral energy distribution (SED) with a strong flux-drop at 8000 Å (4000 Å rest-frame) suggesting an unusually steep extinction curve. By analysing the contribution and physical properties of the host galaxy, we here aim at providing additional information on the properties and origin of this steep, non-standard extinction. We find that the strong flux-drop in the GRB afterglow spectrum at contamination by the host galaxy light at short wavelengths so that the scenario with an extreme 2175 Å extinction bump can be excluded. We localise the GRB to be at a projected distance of approximately 4 kpc from the centre of the host galaxy. Based on emission-line diagnostics of the four detected nebular lines, Hα, Hβ, [O II] and [O III], we find the host to be a modestly star forming (SFR = 1.34 ± 0.04 M⊙ yr-1) and relatively metal poor (Z=0.35+0.15-0.11 Z⊙) galaxy with a large dust content, characterised by a measured visual attenuation of AV = 1.74 ± 0.41 mag. We compare the host to other GRB hosts at similar redshifts and find that it is unexceptional in all its physical properties. We model the extinction curve of the host-corrected afterglow and show that the standard dust properties causing the reddening seen in the Local Group are inadequate in describing the steep drop. We thus conclude that the steep extinction curve seen in the afterglow towards the GRB is of exotic origin and issightline-dependent only, further confirming that this type of reddening is present only at very local scales and that it is solely a consequence of the circumburst environment. Based on observations carried out under programme IDs 095.D-0043(A, C) and 095.A-0045(A) with the X-shooter spectrograph and the FOcal Reducer and low dispersion Spectrograph 2 (FORS2

  1. Essential Structural and Functional Roles of the Cmr4 Subunit in RNA Cleavage by the Cmr CRISPR-Cas Complex

    Directory of Open Access Journals (Sweden)

    Nancy F. Ramia

    2014-12-01

    Full Text Available Summary: The Cmr complex is the multisubunit effector complex of the type III-B clustered regularly interspaced short palindromic repeats (CRISPR-Cas immune system. The Cmr complex recognizes a target RNA through base pairing with the integral CRISPR RNA (crRNA and cleaves the target at multiple regularly spaced locations within the complementary region. To understand the molecular basis of the function of this complex, we have assembled information from electron microscopic and X-ray crystallographic structural studies and mutagenesis of a complete Pyrococcus furiosus Cmr complex. Our findings reveal that four helically packed Cmr4 subunits, which make up the backbone of the Cmr complex, act as a platform to support crRNA binding and target RNA cleavage. Interestingly, we found a hook-like structural feature associated with Cmr4 that is likely the site of target RNA binding and cleavage. Our results also elucidate analogies in the mechanisms of crRNA and target molecule binding by the distinct Cmr type III-A and Cascade type I-E complexes. : Ramia et al. show that the helical core of the type III-B Cmr CRISPR-Cas effector complex, made up of multiple Cmr4 subunits, forms the platform for a corresponding number of cleavages of the target RNA. Comparison with the type I-E Cascade structure reveals strikingly similar mechanisms of crRNA and target binding.

  2. Targeted cleavage of hepatitis E virus 3' end RNA mediated by hammerhead ribozymes inhibits viral RNA replication

    International Nuclear Information System (INIS)

    Sriram, Bandi; Thakral, Deepshi; Panda, Subrat Kumar

    2003-01-01

    The 3' end of hepatitis E virus (HEV) contains cis-acting regulatory element, which plays an important role in viral replication. To develop specific replication inhibitor at the molecular level, mono- and di-hammerhead ribozymes (Rz) were designed and synthesized against the conserved 3' end sequences of HEV, which cleave at nucleotide positions 7125 and 7112/7125, respectively. Di-hammerhead ribozyme with two catalytic motifs in tandem was designed to cleave simultaneously at two sites spaced 13 nucleotides apart, which increases the overall cleavage efficiency and prevents the development of escape mutants. Specific cleavage products were obtained with both the ribozymes in vitro at physiological conditions. The inactive control ribozymes showed no cleavage. The ribozymes showed specific inhibition of HEV 3' end fused-luciferase reporter gene expression by ∼37 and ∼60%, respectively in HepG2 cells. These results demonstrate a feasible approach to inhibit the HEV replication to a limited extent by targeting the cis-acting 3' end of HEV with hammerhead ribozymes

  3. In vitro measurement of beta-carotene cleavage activity : methodological considerations and the effect of other carotenoids on beta-carotene cleavage

    NARCIS (Netherlands)

    Vliet, T. van; Schaik, F. van; Schreurs, W.H.P.; Berg, H. van den

    1996-01-01

    In view of controversies about assessment of the β-carotene cleavage activity, methodological aspects and problems of the dioxygenase assay are described. Using rat and hamster intestinal preparations the method was optimized on retinal formation, the only cleavage product we could demonstrate. It

  4. The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single-Molecule FRET

    Directory of Open Access Journals (Sweden)

    Mengyi Yang

    2018-01-01

    Full Text Available Summary: Off-target binding and cleavage by Cas9 pose major challenges in its application. How the conformational dynamics of Cas9 govern its nuclease activity under on- and off-target conditions remains largely unknown. Here, using intra-molecular single-molecule fluorescence resonance energy transfer measurements, we revealed that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits among three major conformational states, mainly reflecting significant conformational mobility of the catalytic HNH domain. We also uncovered surprising long-range allosteric communication between the HNH domain and the RNA/DNA heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic site, which demonstrated that a unique proofreading mechanism served as the last checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the allosteric communication and proofreading step. Modulating interactions between Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these sites provides an alternative route to improve and optimize the CRISPR/Cas9 toolbox. : Yang et al. revealed significant conformational dynamics of Cas9 at global and local scales using single-molecule FRET. They uncovered surprising long-range allosteric communication between the HNH nuclease domain and the RNA/DNA heteroduplex at the PAM-distal end that serves as a proofreading checkpoint to govern the nuclease activity and specificity of Cas9. Keywords: CRISPR, Cas9, single-molecule, FRET, conformational dynamics, proofreading, off-target, allosteric communication, genome editing

  5. Optical light curve of GRB 121011A: a textbook for the onset of GRB afterglow in a mixture of ISM and wind-type medium

    International Nuclear Information System (INIS)

    Xin, Li-Ping; Wei, Jian-Yan; Qiu, Yu-Lei; Deng, Jin-Song; Wang, Jing; Han, Xu-Hui

    2016-01-01

    We report the optical observations of GRB 121011A by the 0.8m TNT facility at Xinglong observatory, China. The light curve of the optical afterglow shows a smooth and featureless bump during the epoch of ∼130 s and ∼5000 s with a rising index of 1.57 ± 0.28 before the break time of 539 ± 44 s, and a decaying index of about 1.29 ± 0.07 up to the end of our observations. Moreover, the X-ray light curve decays in a single power-law with a slope of about 1.51 ± 0.03 observed by XRT onboard Swift from 100 s to about 10 000 s after the burst trigger. The featureless optical light curve could be understood as an onset process under the external-shock model. The typical frequency has been below or near the optical one before the deceleration time, and the cooling frequency is located between the optical and X-ray wavelengths. The external medium density has a transition from a mixed stage of ISM and wind-type medium before the peak time to the ISM at the later phase. The joint-analysis of X-ray and optical light curves shows that the emissions from both frequencies are consistent with the prediction of the standard afterglow model without any energy injections, indicating that the central engine has stopped its activity and does not restart anymore after the prompt phase. (paper)

  6. Carotenoid-cleavage activities of crude enzymes from Pandanous amryllifolius.

    Science.gov (United States)

    Ningrum, Andriati; Schreiner, Matthias

    2014-11-01

    Carotenoid degradation products, known as norisoprenoids, are aroma-impact compounds in several plants. Pandan wangi is a common name of the shrub Pandanus amaryllifolius. The genus name 'Pandanus' is derived from the Indonesian name of the tree, pandan. In Indonesia, the leaves from the plant are used for several purposes, e.g., as natural colorants and flavor, and as traditional treatments. The aim of this study was to determine the cleavage of β-carotene and β-apo-8'-carotenal by carotenoid-cleavage enzymes isolated from pandan leaves, to investigate dependencies of the enzymatic activities on temperature and pH, to determine the enzymatic reaction products by using Headspace Solid Phase Microextraction Gas Chromatography/Mass Spectrophotometry (HS-SPME GC/MS), and to investigate the influence of heat treatment and addition of crude enzyme on formation of norisoprenoids. Crude enzymes from pandan leaves showed higher activity against β-carotene than β-apo-8'-carotenal. The optimum temperature of crude enzymes was 70°, while the optimum pH value was 6. We identified β-ionone as the major volatile reaction product from the incubations of two different carotenoid substrates, β-carotene and β-apo-8'-carotenal. Several treatments, e.g., heat treatment and addition of crude enzymes in pandan leaves contributed to the norisoprenoid content. Our findings revealed that the crude enzymes from pandan leaves with carotenoid-cleavage activity might provide a potential application, especially for biocatalysis, in natural-flavor industry. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

  7. High cleavage efficiency of a 2A peptide derived from porcine teschovirus-1 in human cell lines, zebrafish and mice.

    Directory of Open Access Journals (Sweden)

    Jin Hee Kim

    Full Text Available When expression of more than one gene is required in cells, bicistronic or multicistronic expression vectors have been used. Among various strategies employed to construct bicistronic or multicistronic vectors, an internal ribosomal entry site (IRES has been widely used. Due to the large size and difference in expression levels between genes before and after IRES, however, a new strategy was required to replace IRES. A self-cleaving 2A peptide could be a good candidate to replace IRES because of its small size and high cleavage efficiency between genes upstream and downstream of the 2A peptide. Despite the advantages of the 2A peptides, its use is not widespread because (i there are no publicly available cloning vectors harboring a 2A peptide gene and (ii comprehensive comparison of cleavage efficiency among various 2A peptides reported to date has not been performed in different contexts. Here, we generated four expression plasmids each harboring different 2A peptides derived from the foot-and-mouth disease virus, equine rhinitis A virus, Thosea asigna virus and porcine teschovirus-1, respectively, and evaluated their cleavage efficiency in three commonly used human cell lines, zebrafish embryos and adult mice. Western blotting and confocal microscopic analyses revealed that among the four 2As, the one derived from porcine teschovirus-1 (P2A has the highest cleavage efficiency in all the contexts examined. We anticipate that the 2A-harboring cloning vectors we generated and the highest efficiency of the P2A peptide we demonstrated would help biomedical researchers easily adopt the 2A technology when bicistronic or multicistronic expression is required.

  8. Structural and functional characterization of cleavage and inactivation of human serine protease inhibitors by the bacterial SPATE protease EspPα from enterohemorrhagic E. coli.

    Directory of Open Access Journals (Sweden)

    André Weiss

    Full Text Available EspPα and EspI are serine protease autotransporters found in enterohemorrhagic Escherichia coli. They both belong to the SPATE autotransporter family and are believed to contribute to pathogenicity via proteolytic cleavage and inactivation of different key host proteins during infection. Here, we describe the specific cleavage and functional inactivation of serine protease inhibitors (serpins by EspPα and compare this activity with the related SPATE EspI. Serpins are structurally related proteins that regulate vital protease cascades, such as blood coagulation and inflammatory host response. For the rapid determination of serpin cleavage sites, we applied direct MALDI-TOF-MS or ESI-FTMS analysis of coincubations of serpins and SPATE proteases and confirmed observed cleavage positions using in-gel-digest of SDS-PAGE-separated degradation products. Activities of both serpin and SPATE protease were assessed in a newly developed photometrical assay using chromogenic peptide substrates. EspPα cleaved the serpins α1-protease inhibitor (α1-PI, α1-antichymotrypsin, angiotensinogen, and α2-antiplasmin. Serpin cleavage led to loss of inhibitory function as demonstrated for α1-PI while EspPα activity was not affected. Notably, EspPα showed pronounced specificity and cleaved procoagulatory serpins such as α2-antiplasmin while the anticoagulatory antithrombin III was not affected. Together with recently published research, this underlines the interference of EspPα with hemostasis or inflammatory responses during infection, while the observed interaction of EspI with serpins is likely to be not physiologically relevant. EspPα-mediated serpin cleavage occurred always in flexible loops, indicating that this structural motif might be required for substrate recognition.

  9. LFsGRB: Binary neutron star merger rate via the luminosity function of short gamma-ray bursts

    Science.gov (United States)

    Paul, Debdutta

    2018-04-01

    LFsGRB models the luminosity function (LF) of short Gamma Ray Bursts (sGRBs) by using the available catalog data of all short GRBs (sGRBs) detected till 2017 October, estimating the luminosities via pseudo-redshifts obtained from the Yonetoku correlation, and then assuming a standard delay distribution between the cosmic star formation rate and the production rate of their progenitors. The data are fit well both by exponential cutoff powerlaw and broken powerlaw models. Using the derived parameters of these models along with conservative values in the jet opening angles seen from afterglow observations, the true rate of short GRBs is derived. Assuming a short GRB is produced from each binary neutron star merger (BNSM), the rate of gravitational wave (GW) detections from these mergers are derived for the past, present and future configurations of the GW detector networks.

  10. EARLY-TIME VLA OBSERVATIONS AND BROADBAND AFTERGLOW ANALYSIS OF THE FERMI/LAT DETECTED GRB 130907A

    International Nuclear Information System (INIS)

    Veres, Péter; Corsi, Alessandra; Frail, Dale A.; Cenko, S. Bradley; Perley, Daniel A.

    2015-01-01

    We present multi-wavelength observations of the hyper-energetic gamma-ray burst (GRB) 130907A, a Swift-discovered burst with early radio observations starting at ≈4 hr after the γ-ray trigger. GRB 130907A was also detected by the Fermi/LAT instrument and at late times showed a strong spectral evolution in X-rays. We focus on the early-time radio observations, especially at >10 GHz, to attempt to identify reverse shock signatures. While our radio follow-up of GRB 130907A ranks among the earliest observations of a GRB with the Karl G. Jansky Very Large Array, we did not see an unambiguous signature of a reverse shock. While a model with both reverse and forward shock can correctly describe the observations, the data is not constraining enough to decide upon the presence of the reverse-shock component. We model the broadband data using a simple forward-shock synchrotron scenario with a transition from a wind environment to a constant density interstellar medium (ISM) in order to account for the observed features. Within the confines of this model, we also derive the underlying physical parameters of the fireball, which are within typical ranges except for the wind density parameter (A * ), which is higher than those for bursts with wind-ISM transition, but typical for the general population of bursts. We note the importance of early-time radio observations of the afterglow (and of well-sampled light curves) for unambiguously identifying the potential contribution of the reverse shock

  11. Hubble Space Telescope Observations of the Afterglow, Supernova and Host Galaxy Associated with the Extremely Bright GRB 130427A

    Science.gov (United States)

    Levan, A.J.; Tanvir, N. R.; Fruchter, A. S.; Hjorth, J.; Pian, E.; Mazzali, P.; Hounsell, R. A.; Perley, D. A.; Cano, Z.; Graham, J.; hide

    2014-01-01

    We present Hubble Space Telescope (HST) observations of the exceptionally bright and luminous Swift gamma-ray burst, GRB 130427A. At z=0.34 this burst affords an excellent opportunity to study the supernova and host galaxy associated with an intrinsically extremely luminous burst (E(sub iso) greater than 10(exp 54) erg): more luminous than any previous GRB with a spectroscopically associated supernova. We use the combination of the image quality, UV capability and and invariant PSF of HST to provide the best possible separation of the afterglow, host and supernova contributions to the observed light approximately 17 rest-frame days after the burst utilising a host subtraction spectrum obtained 1 year later. Advanced Camera for Surveys (ACS) grism observations show that the associated supernova, SN 2013cq, has an overall spectral shape and luminosity similar to SN 1998bw (with a photospheric velocity, vph approximately 15,000 kilometers per second). The positions of the bluer features are better matched by the higher velocity SN 2010bh (vph approximately 30,000 kilometers per second), but SN 2010bh (vph approximately 30,000 kilometers per second but this SN is significantly fainter, and fails to reproduce the overall spectral shape, perhaps indicative of velocity structure in the ejecta. We find that the burst originated approximately 4 kpc from the nucleus of a moderately star forming (1 Solar Mass yr(exp-1)), possibly interacting disc galaxy. The absolute magnitude, physical size and morphology of this galaxy, as well as the location of the GRB within it are also strikingly similar to those of GRB980425SN 1998bw. The similarity of supernovae and environment from both the most luminous and least luminous GRBs suggests broadly similar progenitor stars can create GRBs across six orders of magnitude in isotropic energy.

  12. Grb-IR: A SH2-Domain-Containing Protein that Binds to the Insulin Receptor and Inhibits Its Function

    Science.gov (United States)

    Liu, Feng; Roth, Richard A.

    1995-10-01

    To identify potential signaling molecules involved in mediating insulin-induced biological responses, a yeast two-hybrid screen was performed with the cytoplasmic domain of the human insulin receptor (IR) as bait to trap high-affinity interacting proteins encoded by human liver or HeLa cDNA libraries. A SH2-domain-containing protein was identified that binds with high affinity in vitro to the autophosphorylated IR. The mRNA for this protein was found by Northern blot analyses to be highest in skeletal muscle and was also detected in fat by PCR. To study the role of this protein in insulin signaling, a full-length cDNA encoding this protein (called Grb-IR) was isolated and stably expressed in Chinese hamster ovary cells overexpressing the human IR. Insulin treatment of these cells resulted in the in situ formation of a complex of the IR and the 60-kDa Grb-IR. Although almost 75% of the Grb-IR protein was bound to the IR, it was only weakly tyrosine-phosphorylated. The formation of this complex appeared to inhibit the insulin-induced increase in tyrosine phosphorylation of two endogenous substrates, a 60-kDa GTPase-activating-protein-associated protein and, to a lesser extent, IR substrate 1. The subsequent association of this latter protein with phosphatidylinositol 3-kinase also appeared to be inhibited. These findings raise the possibility that Grb-IR is a SH2-domain-containing protein that directly complexes with the IR and serves to inhibit signaling or redirect the IR signaling pathway.

  13. Caspase-2 cleavage of tau reversibly impairs memory.

    Science.gov (United States)

    Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H

    2016-11-01

    In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.

  14. Comparison of the cleavage of pyrimidine dimers by the bacteriophage T4 and Micrococcus luteus uv-specific endonucleases

    International Nuclear Information System (INIS)

    Gordon, L.K.; Haseltine, W.A.

    1980-01-01

    A comparison was made of the activity of the uv-specific endonucleases of bacteriophage T4 (T4 endonuclease V) and of Micrococcus luteus on ultraviolet light-irradiated DNA substrates of defined sequence. The two enzyms cleave DNA at the site of pyrimidine dimers with the same frequency. The products of the cleavage reaction are the same. The pyrimidine dimer DNA-glycosylase activity of both enzymes is more active on double-stranded DNA than it is on single-stranded DNA

  15. Evaluating the Bulk Lorentz Factors of Outflow Material: Lessons Learned from the Extremely Energetic Outburst GRB 160625B

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuan-Zhu; Wang, Hao; Zhang, Shuai; Liang, Yun-Feng; Jin, Zhi-Ping; He, Hao-Ning; Liao, Neng-Hui; Fan, Yi-Zhong; Wei, Da-Ming, E-mail: liangyf@pmo.ac.cn, E-mail: jin@pmo.ac.cn, E-mail: dmwei@pmo.ac.cn [Key Laboratory of Dark Matter and Space Astronomy, Purple Mountain Observatory, Chinese Academy of Science, Nanjing, 210008 (China)

    2017-02-10

    GRB 160625B is an extremely bright outburst with well-monitored afterglow emission. The geometry-corrected energy is high, up to ∼5.2 × 10{sup 52} erg or even ∼8 × 10{sup 52} erg, rendering it the most energetic GRB prompt emission recorded so far. We analyzed the time-resolved spectra of the prompt emission and found that in some intervals there were likely thermal-radiation components and the high energy emission was characterized by significant cutoff. The bulk Lorentz factors of the outflow material are estimated accordingly. We found out that the Lorentz factors derived in the thermal-radiation model are consistent with the luminosity-Lorentz factor correlation found in other bursts, as well as in GRB 090902B for the time-resolved thermal-radiation components, while the spectral cutoff model yields much lower Lorentz factors that are in tension with the constraints set by the electron pair Compton scattering process. We then suggest that these spectral cutoffs are more likely related to the particle acceleration process and that one should be careful in estimating the Lorentz factors if the spectrum cuts at a rather low energy (e.g., ∼tens of MeV). The nature of the central engine has also been discussed, and a stellar-mass black hole is favored.

  16. The Faint Optical Afterglow and Host Galaxy of GRB 020124: Implications for the Nature of Dark Gamma-Ray Bursts

    Science.gov (United States)

    Berger, E.; Kulkarni, S. R.; Bloom, J. S.; Price, P. A.; Fox, D. W.; Frail, D. A.; Axelrod, T. S.; Chevalier, R. A.; Colbert, E.; Costa, E.; Djorgovski, S. G.; Frontera, F.; Galama, T. J.; Halpern, J. P.; Harrison, F. A.; Holtzman, J.; Hurley, K.; Kimble, R. A.; McCarthy, P. J.; Piro, L.; Reichart, D.; Ricker, G. R.; Sari, R.; Schmidt, B. P.; Wheeler, J. C.; Vanderppek, R.; Yost, S. A.

    2002-12-01

    We present ground-based optical observations of GRB 020124 starting 1.6 hr after the burst, as well as subsequent Very Large Array and Hubble Space Telescope (HST) observations. The optical afterglow of GRB 020124 is one of the faintest afterglows detected to date, and it exhibits a relatively rapid decay, Fν~t-1.60+/-0.04, followed by further steepening. In addition, a weak radio source was found coincident with the optical afterglow. The HST observations reveal that a positionally coincident host galaxy must be the faintest host to date, R>~29.5 mag. The afterglow observations can be explained by several models requiring little or no extinction within the host galaxy, AhostV~0-0.9 mag. These observations have significant implications for the interpretation of the so-called dark bursts (bursts for which no optical afterglow is detected), which are usually attributed to dust extinction within the host galaxy. The faintness and relatively rapid decay of the afterglow of GRB 020124, combined with the low inferred extinction, indicate that some dark bursts are intrinsically dim and not dust obscured. Thus, the diversity in the underlying properties of optical afterglows must be observationally determined before substantive inferences can be drawn from the statistics of dark bursts.

  17. Altered cleavage patterns in human tripronuclear embryos and their association to fertilization method

    DEFF Research Database (Denmark)

    Joergensen, Mette Warming; Agerholm, Inge; Hindkjaer, Johnny

    2014-01-01

    PURPOSE: To analyze the cleavage patterns in dipronuclear (2PN) and tripronuclear (3PN) embryos in relation to fertilization method. METHOD: Time-lapse analysis. RESULTS: Compared to 2PN, more 3PN IVF embryos displayed early cleavage into 3 cells (p ... stage (p embryos, the 2nd and 3rd cleavage cycles were completed within the expected time frame. However, timing of the cell divisions within the cleavage cycles differed between the two groups. In contrast......, the completion of the 1st, 2nd, and 3rd cleavage cycle was delayed, but with a similar division pattern for 3PN ICSI compared with the 2PN ICSI embryos. 3PN, more often than 2PN ICSI embryos, displayed early cleavage into 3 cells (p = 0.03) and arrested development from the compaction stage and onwards (p = 0...

  18. Cleavage of phosphorothioated DNA and methylated DNA by the type IV restriction endonuclease ScoMcrA.

    Directory of Open Access Journals (Sweden)

    Guang Liu

    2010-12-01

    Full Text Available Many taxonomically diverse prokaryotes enzymatically modify their DNA by replacing a non-bridging oxygen with a sulfur atom at specific sequences. The biological implications of this DNA S-modification (phosphorothioation were unknown. We observed that simultaneous expression of the dndA-E gene cluster from Streptomyces lividans 66, which is responsible for the DNA S-modification, and the putative Streptomyces coelicolor A(32 Type IV methyl-dependent restriction endonuclease ScoA3McrA (Sco4631 leads to cell death in the same host. A His-tagged derivative of ScoA3McrA cleaved S-modified DNA and also Dcm-methylated DNA in vitro near the respective modification sites. Double-strand cleavage occurred 16-28 nucleotides away from the phosphorothioate links. DNase I footprinting demonstrated binding of ScoA3McrA to the Dcm methylation site, but no clear binding could be detected at the S-modified site under cleavage conditions. This is the first report of in vitro endonuclease activity of a McrA homologue and also the first demonstration of an enzyme that specifically cleaves S-modified DNA.

  19. THE BURST CLUSTER: DARK MATTER IN A CLUSTER MERGER ASSOCIATED WITH THE SHORT GAMMA-RAY BURST, GRB 050509B

    International Nuclear Information System (INIS)

    Dahle, H.; Sarazin, C. L.; Lopez, L. A.; Kouveliotou, C.; Patel, S. K.; Rol, E.; Van der Horst, A. J.; Wijers, R. A. M. J.; Fynbo, J.; Michałowski, M. J.; Burrows, D. N.; Grupe, D.; Gehrels, N.; Ramirez-Ruiz, E.

    2013-01-01

    We have identified a merging galaxy cluster with evidence of two distinct subclusters. The X-ray and optical data suggest that the subclusters are presently moving away from each other after closest approach. This cluster merger was discovered from observations of the first well-localized short-duration gamma-ray burst (GRB), GRB 050509B. The Swift/Burst Alert Telescope error position of the source is coincident with a cluster of galaxies ZwCl 1234.0+02916, while the subsequent Swift/X-Ray Telescope localization of the X-ray afterglow found the GRB coincident with 2MASX J12361286+2858580, a giant red elliptical galaxy in the cluster. Deep multi-epoch optical images were obtained in this field to constrain the evolution of the GRB afterglow, including a total of 27,480 s exposure in the F814W band with Hubble Space Telescope Advanced Camera for Surveys, among the deepest imaging ever obtained toward a known galaxy cluster in a single passband. We perform a weak gravitational lensing analysis based on these data, including mapping of the total mass distribution of the merger system with high spatial resolution. When combined with Chandra X-ray Observatory Advanced CCD Imaging Spectrometer and Swift/XRT observations, we are able to investigate the dynamical state of the merger to better understand the nature of the dark matter component. Our weak gravitational lensing measurements reveal a separation of the X-ray centroid of the western subcluster from the center of the mass and galaxy light distributions, which is somewhat similar to that of the famous 'Bullet cluster', and we conclude that this 'Burst cluster' adds another candidate to the previously known merger systems for determining the nature of dark matter, as well as for studying the environment of a short GRB. Finally, we discuss potential connections between the cluster dynamical state and/or matter composition, and compact object mergers, which is currently the leading model for the origin of short GRBs

  20. THE BURST CLUSTER: DARK MATTER IN A CLUSTER MERGER ASSOCIATED WITH THE SHORT GAMMA-RAY BURST, GRB 050509B

    Energy Technology Data Exchange (ETDEWEB)

    Dahle, H. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029, Blindern, NO-0315 Oslo (Norway); Sarazin, C. L. [Department of Astronomy, University of Virginia, P.O. Box 400325, Charlottesville, VA 22904-4325 (United States); Lopez, L. A. [MIT-Kavli Institute for Astrophysics and Space Research, 77 Massachusetts Avenue, 37-664H, Cambridge, MA 02139 (United States); Kouveliotou, C. [Space Science Office, ZP12, NASA/Marshall Space Flight Center, Huntsville, AL 35812 (United States); Patel, S. K. [Optical Sciences Corporation, 6767 Old Madison Pike, Suite 650, Huntsville, AL 35806 (United States); Rol, E.; Van der Horst, A. J.; Wijers, R. A. M. J. [Astronomical Institute ' Anton Pannekoek' , University of Amsterdam, Kruislaan 403, 1098 SJ Amsterdam (Netherlands); Fynbo, J.; Michalowski, M. J. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries vej 30, DK-2100 Copenhagen (Denmark); Burrows, D. N.; Grupe, D. [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Gehrels, N. [NASA/Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Ramirez-Ruiz, E., E-mail: hdahle@astro.uio.no [Department of Astronomy and Astrophysics, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95060 (United States)

    2013-07-20

    We have identified a merging galaxy cluster with evidence of two distinct subclusters. The X-ray and optical data suggest that the subclusters are presently moving away from each other after closest approach. This cluster merger was discovered from observations of the first well-localized short-duration gamma-ray burst (GRB), GRB 050509B. The Swift/Burst Alert Telescope error position of the source is coincident with a cluster of galaxies ZwCl 1234.0+02916, while the subsequent Swift/X-Ray Telescope localization of the X-ray afterglow found the GRB coincident with 2MASX J12361286+2858580, a giant red elliptical galaxy in the cluster. Deep multi-epoch optical images were obtained in this field to constrain the evolution of the GRB afterglow, including a total of 27,480 s exposure in the F814W band with Hubble Space Telescope Advanced Camera for Surveys, among the deepest imaging ever obtained toward a known galaxy cluster in a single passband. We perform a weak gravitational lensing analysis based on these data, including mapping of the total mass distribution of the merger system with high spatial resolution. When combined with Chandra X-ray Observatory Advanced CCD Imaging Spectrometer and Swift/XRT observations, we are able to investigate the dynamical state of the merger to better understand the nature of the dark matter component. Our weak gravitational lensing measurements reveal a separation of the X-ray centroid of the western subcluster from the center of the mass and galaxy light distributions, which is somewhat similar to that of the famous 'Bullet cluster', and we conclude that this 'Burst cluster' adds another candidate to the previously known merger systems for determining the nature of dark matter, as well as for studying the environment of a short GRB. Finally, we discuss potential connections between the cluster dynamical state and/or matter composition, and compact object mergers, which is currently the leading model for the

  1. Embryo apoptosis identification: Oocyte grade or cleavage stage?

    Science.gov (United States)

    Bakri, Noraina Mohd; Ibrahim, Siti Fatimah; Osman, Nurul Atikah; Hasan, Nurhaslina; Jaffar, Farah Hanan Fathihah; Rahman, Zulaiha Abdul; Osman, Khairul

    2015-01-01

    Apoptosis is a programed cell death that is vital for tissue homeostasis. However, embryo apoptosis had been known to be related to embryo fragmentation which should be avoided in in vitro fertilization (IVF). The purpose of this study was to evaluate the relationship of embryo apoptosis with the grade of immature oocytes and cleavage stage of in vitro produced (IVP) cattle embryos. This study consisted of 345 oocytes collected through ovary slicing. Immature oocytes were graded as A, B and C. This grading was based on cumulus cell thickness and compactness. All oocytes then underwent an in vitro maturation (IVM) procedure. An IVF was done 24 h after IVM culture. Prior to staining, stage of cleaved embryos was determined and classified as either 2, 4, 8 or >8-cell embryo stage. Apoptosis status of cleaved IVP embryos was determined by using annexin V-FITC staining technique at 48 and 72 h post insemination (hpi). Apoptosis status for each embryo was classified as either early or late. The result showed that there was no significant difference (p > 0.05) of apoptosis status among grade A, B and C embryos. All grades of oocytes showed embryo apoptosis where 1.5% late apoptosis for grade A, 4.5% and 10.4% of early and late apoptosis for grade B and grade C. Early apoptosis was not seen in grade A embryo. We also noted no significant difference (p > 0.05) of apoptosis status between 2, 4, 8 and >8-cell embryo stage. Early apoptosis was also not seen in >8-cell stage. Even though there were no differences in apoptosis expression between the three classes, the cleavage rate of grade A oocytes was significantly higher (p < 0.01) than grade B and grade C. In conclusion, the apoptosis expression in the embryo can occur regardless of the oocyte quality and the cleavage stage of the embryo produced. PMID:26858565

  2. Single-Molecule Analysis for RISC Assembly and Target Cleavage.

    Science.gov (United States)

    Sasaki, Hiroshi M; Tadakuma, Hisashi; Tomari, Yukihide

    2018-01-01

    RNA-induced silencing complex (RISC) is a small RNA-protein complex that mediates silencing of complementary target RNAs. Biochemistry has been successfully used to characterize the molecular mechanism of RISC assembly and function for nearly two decades. However, further dissection of intermediate states during the reactions has been warranted to fill in the gaps in our understanding of RNA silencing mechanisms. Single-molecule analysis with total internal reflection fluorescence (TIRF) microscopy is a powerful imaging-based approach to interrogate complex formation and dynamics at the individual molecule level with high sensitivity. Combining this technique with our recently established in vitro reconstitution system of fly Ago2-RISC, we have developed a single-molecule observation system for RISC assembly. In this chapter, we summarize the detailed protocol for single-molecule analysis of chaperone-assisted assembly of fly Ago2-RISC as well as its target cleavage reaction.

  3. 3' RNA ligase mediated rapid amplification of cDNA ends for validating viroid induced cleavage at the 3' extremity of the host mRNA.

    Science.gov (United States)

    Adkar-Purushothama, Charith Raj; Bru, Pierrick; Perreault, Jean-Pierre

    2017-12-01

    5' RNA ligase-mediated rapid amplification of cDNA ends (5' RLM-RACE) is a widely-accepted method for the validation of direct cleavage of a target gene by a microRNA (miRNA) and viroid-derived small RNA (vd-sRNA). However, this method cannot be used if cleavage takes place in the 3' extremity of the target RNA, as this gives insufficient sequence length to design nested PCR primers for 5' RLM RACE. To overcome this hurdle, we have developed 3' RNA ligase-mediated rapid amplification of cDNA ends (3' RLM RACE). In this method, an oligonucleotide adapter having 5' adenylated and 3' blocked is ligated to the 3' end of the cleaved RNA followed by PCR amplification using gene specific primers. In other words, in 3' RLM RACE, 3' end is mapped using 5' fragment instead of small 3' fragment. The method developed here was verified by examining the bioinformatics predicted and parallel analysis of RNA ends (PARE) proved cleavage sites of chloride channel protein CLC-b-like mRNA in Potato spindle tuber viroid infected tomato plants. The 3' RLM RACE developed in this study has the potential to validate the miRNA and vd-sRNA mediated cleavage of mRNAs at its 3' untranslated region (3' UTR). Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Proteolytic processing of the cilium adhesin MHJ_0194 (P123J ) in Mycoplasma hyopneumoniae generates a functionally diverse array of cleavage fragments that bind multiple host molecules.

    Science.gov (United States)

    Raymond, Benjamin B A; Jenkins, Cheryl; Seymour, Lisa M; Tacchi, Jessica L; Widjaja, Michael; Jarocki, Veronica M; Deutscher, Ania T; Turnbull, Lynne; Whitchurch, Cynthia B; Padula, Matthew P; Djordjevic, Steven P

    2015-03-01

    Mycoplasma hyopneumoniae, the aetiological agent of porcine enzootic pneumonia, regulates the presentation of proteins on its cell surface via endoproteolysis, including those of the cilial adhesin P123 (MHJ_0194). These proteolytic cleavage events create functional adhesins that bind to proteoglycans and glycoproteins on the surface of ciliated and non-ciliated epithelial cells and to the circulatory host molecule plasminogen. Two dominant cleavage events of the P123 preprotein have been previously characterized; however, immunoblotting studies suggest that more complex processing events occur. These extensive processing events are characterized here. The functional significance of the P97 cleavage fragments is also poorly understood. Affinity chromatography using heparin, fibronectin and plasminogen as bait and peptide arrays were used to expand our knowledge of the adhesive capabilities of P123 cleavage fragments and characterize a novel binding motif in the C-terminus of P123. Further, we use immunohistochemistry to examine in vivo, the biological significance of interactions between M. hyopneumoniae and fibronectin and show that M. hyopneumoniae induces fibronectin deposition at the site of infection on the ciliated epithelium. Our data supports the hypothesis that M. hyopneumoniae possesses the molecular machinery to influence key molecular communication pathways in host cells. © 2014 John Wiley & Sons Ltd.

  5. Ultrarapid mutation detection by multiplex, solid-phase chemical cleavage

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, G.; Saad, S.; Giannelli, F.; Green, P.M. [Guy`s & St. Thomas`s Hospitals, London (United Kingdom)

    1995-12-10

    The chemical cleavage of mismatches in heteroduplexes formed by probe and test DNA detects and locates any sequence change in long DNA segments ({approximately}1.8 kb), and its efficiency has been well tested in the analysis of both average (e.g., coagulation factor IX) and large, complex genes (e.g., coagulation factor VIII and dystrophin). In the latter application RT/PCR products allow the examination of all essential sequences of the gene in a minimum number of reactions. We use two specific chemical reactants (hydroxylamine and osmium tetroxide) and piperidine cleavage of the above procedure to develop a very fast mutation screening method. This is based on: (1) 5{prime} or internal fluorescent labeling to allow concurrent screening of three to four DNA fragments and (2) solid-phase chemistry to use a microliter format and reduce the time required for the procedure, from amplification of sequence to gel loading inclusive, to one person-working-day. We test the two variations of the method, one entailing 5{prime} labeling of probe DNA and the other uniform labeling of both probe and target DNA, by detecting 114 known hemophilia B (coagulation factor IX) mutations and by analyzing 129 new patients. Uniform labeling of both probe and target DNA prior to formation of the heteroduplexes leads to almost twofold redundancy in the ability to detect mutations. Alternatively, the latter procedure may offer very efficient though less than 100% screening for sequence changes with only hydroxylamine. The full method with two chemical reactions (hydroxylamine and osmium tetroxide) should allow one person to screen with virtually 100% accuracy more than 300 kb of sequence in three ABI 373 gels in 1 day. 26 refs., 7 figs., 1 tab.

  6. Modelling of ductile and cleavage fracture by local approach

    International Nuclear Information System (INIS)

    Samal, M.K.; Dutta, B.K.; Kushwaha, H.S.

    2000-08-01

    This report describes the modelling of ductile and cleavage fracture processes by local approach. It is now well known that the conventional fracture mechanics method based on single parameter criteria is not adequate to model the fracture processes. It is because of the existence of effect of size and geometry of flaw, loading type and rate on the fracture resistance behaviour of any structure. Hence, it is questionable to use same fracture resistance curves as determined from standard tests in the analysis of real life components because of existence of all the above effects. So, there is need to have a method in which the parameters used for the analysis will be true material properties, i.e. independent of geometry and size. One of the solutions to the above problem is the use of local approaches. These approaches have been extensively studied and applied to different materials (including SA33 Gr.6) in this report. Each method has been studied and reported in a separate section. This report has been divided into five sections. Section-I gives a brief review of the fundamentals of fracture process. Section-II deals with modelling of ductile fracture by locally uncoupled type of models. In this section, the critical cavity growth parameters of the different models have been determined for the primary heat transport (PHT) piping material of Indian pressurised heavy water reactor (PHWR). A comparative study has been done among different models. The dependency of the critical parameters on stress triaxiality factor has also been studied. It is observed that Rice and Tracey's model is the most suitable one. But, its parameters are not fully independent of triaxiality factor. For this purpose, a modification to Rice and Tracery's model is suggested in Section-III. Section-IV deals with modelling of ductile fracture process by locally coupled type of models. Section-V deals with the modelling of cleavage fracture process by Beremins model, which is based on Weibulls

  7. Micromechanisms and toughness for cleavage fracture of steel

    International Nuclear Information System (INIS)

    Rosenfield, A.R.; Majumdar, B.S.

    1987-01-01

    A complete understanding of the fracture mechanisms of steel in the ductile/brittle transition region requires analysis not only of crack initiation, but also of crack propagation. This paper reviews micrographic and fractographic experiments that give insight into both phenomena, and suggests a frame-work through which both may be related. Unstable cleavage crack initiation can occur after some blunting of the original fatigue precrack or after some stable crack growth. In either event, instability appears to be triggered by the fracture of a brittle micro-constituent ahead of the precrack. The large scatter in reported K IC values within the transition region reflects the size distribution and relative scarcity of these 'trigger' particles. While a large number of models have attempted to correlate toughness in the ductile/brittle transition regime to events occurring ahead of the crack tip, surprisingly little attention has been paid to events occurring behind the crack front. Fractographic evidence as well as metallographic sectioning of arrested cracks show that the mechanism of rapid crack propagation by cleavage is affected strongly by partial crack-plane deflection which leaves unbroken ligaments in its wake. The tearing of these ligaments by dimple-rupture is the dominant energy-absorbing mechanism. Etch-pit experiments using an Fe-Si alloy show that the crack-tip stress intensity based on plastic zone size is extremely low. It is suggested that the mechanism of crack arrest should be modeled using a sharp crack which is restrained by a distribution of discrete pinching forces along its faces. The same model is applied to crack initiation. (orig.)

  8. Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2

    DEFF Research Database (Denmark)

    VanderKuur, J; Allevato, G; Billestrup, Nils

    1995-01-01

    . To gain insight into pathways coupling GH receptor (GHR) to MAP kinase activation and signaling molecules that might interact with GHR and its associated tyrosine kinase JAK2, we examined whether SHC and Grb2 proteins serve as signaling molecules for GH. Human GH was shown to promote the rapid tyrosyl...... phosphorylation of 66-, 52-, and 46-kDa SHC proteins in 3T3-F442A fibroblasts. GH also promoted binding of GHR and JAK2 to the SH2 domain of 46/52-kDa SHC protein fused to glutathione S-transferase (GST). Constitutively phosphorylated JAK2, from COS-7 cells transiently transfected with murine JAK2 cDNA, bound......-638 and GHR1-638(Y333,338F), GH stimulated phosphorylation of all 3 SHC proteins whereas GH stimulated phosphorylation of only the 66- and 52-kDa SHC proteins in cells expressing GHR1-454. GH had no effect on SHC phosphorylation in cells expressing GHR1-294 or GHR delta P, the latter lacking amino acids 297...

  9. The afterglow and elliptical host galaxy of the short gamma-ray burst GRB 050724.

    Science.gov (United States)

    Berger, E; Price, P A; Cenko, S B; Gal-Yam, A; Soderberg, A M; Kasliwal, M; Leonard, D C; Cameron, P B; Frail, D A; Kulkarni, S R; Murphy, D C; Krzeminski, W; Piran, T; Lee, B L; Roth, K C; Moon, D-S; Fox, D B; Harrison, F A; Persson, S E; Schmidt, B P; Penprase, B E; Rich, J; Peterson, B A; Cowie, L L

    2005-12-15

    Despite a rich phenomenology, gamma-ray bursts (GRBs) are divided into two classes based on their duration and spectral hardness--the long-soft and the short-hard bursts. The discovery of afterglow emission from long GRBs was a watershed event, pinpointing their origin to star-forming galaxies, and hence the death of massive stars, and indicating an energy release of about 10(51) erg. While theoretical arguments suggest that short GRBs are produced in the coalescence of binary compact objects (neutron stars or black holes), the progenitors, energetics and environments of these events remain elusive despite recent localizations. Here we report the discovery of the first radio afterglow from the short burst GRB 050724, which unambiguously associates it with an elliptical galaxy at a redshift z = 0.257. We show that the burst is powered by the same relativistic fireball mechanism as long GRBs, with the ejecta possibly collimated in jets, but that the total energy release is 10-1,000 times smaller. More importantly, the nature of the host galaxy demonstrates that short GRBs arise from an old (> 1 Gyr) stellar population, strengthening earlier suggestions and providing support for coalescing compact object binaries as the progenitors.

  10. GRB 110530A: Peculiar Broad Bump and Delayed Plateau in Early Optical Afterglows

    Science.gov (United States)

    Zhong, Shu-Qing; Xin, Li-Ping; Liang, En-Wei; Wei, Jian-Yan; Urata, Yuji; Huang, Kui-Yun; Qiu, Yu-Lei; Deng, Can-Min; Wang, Yuan-Zhu; Deng, Jin-Song

    2016-11-01

    We report our very early optical observations of GRB 110530A and investigate its jet properties together with its X-ray afterglow data. A peculiar broad onset bump followed by a plateau is observed in its early R band afterglow light curve. The optical data in the other bands and the X-ray data are well consistent with the temporal feature of the R band light curve. Our joint spectral fits of the optical and X-ray data show that they are in the same regime, with a photon index of ∼1.70. The optical and X-ray afterglow light curves are well fitted with the standard external shock model by considering a delayed energy injection component. Based on our modeling results, we find that the radiative efficiency of the gamma-ray burst jet is ∼ 1 % and the magnetization parameter of the afterglow jet is \\lt 0.04 with a derived extremely low {ε }B (the ratio of shock energy to the magnetic field) of (1.64+/- 0.25)× {10}-6. These results indicate that the jet may be matter dominated. A discussion on delayed energy injection from the accretion of the late fall-back material of its pre-supernova star is also presented.

  11. A New Era of Submillimeter GRB Afterglow Follow-Ups with the Greenland Telescope

    Directory of Open Access Journals (Sweden)

    Yuji Urata

    2015-01-01

    Full Text Available Planned rapid submillimeter (submm gamma-ray-bursts (GRBs follow-up observations conducted using the Greenland Telescope (GLT are presented. The GLT is a 12-m submm telescope to be located at the top of the Greenland ice sheet, where the high altitude and dry weather porvide excellent conditions for observations at submm wavelengths. With its combination of wavelength window and rapid responding system, the GLT will explore new insights on GRBs. Summarizing the current achievements of submm GRB follow-ups, we identify the following three scientific goals regarding GRBs: (1 systematic detection of bright submm emissions originating from reverse shock (RS in the early afterglow phase, (2 characterization of forward shock and RS emissions by capturing their peak flux and frequencies and performing continuous monitoring, and (3 detections of GRBs at a high redshift as a result of the explosion of first generation stars through systematic rapid follow-ups. The light curves and spectra calculated by available theoretical models clearly show that the GLT could play a crucial role in these studies.

  12. A New Era of Submillimeter GRB Afterglow Follow-Ups with the Greenland Telescope

    Science.gov (United States)

    Urata, Yuji; Huang, Kuiyun; Asada, Keiichi; Hirashita, Hiroyuki; Inoue, Makoto; Ho, Paul T. P.

    A planned rapid submillimeter (submm) Gamma Ray Burst (GRBs) follow-up observations conducted using the Greenland Telescope (GLT) is presented. The GLT is a 12-m submm telescope to be located at the top of the Greenland ice sheet, where the high-altitude and dry weather porvides excellent conditions for observations at submm wavelengths. With its combination of wavelength window and rapid responding system, the GLT will explore new insights on GRBs. Summarizing the current achievements of submm GRB follow-ups, we identify the following three scientific goals regarding GRBs: (1) systematic detection of bright submm emissions originating from reverse shock (RS) in the early afterglow phase, (2) characterization of forward shock and RS emissions by capturing their peak flux and frequencies and performing continuous monitoring, and (3) detections of GRBs as a result of the explosion of first-generation stars result of GRBs at a high redshift through systematic rapid follow ups. The light curves and spectra calculated by available theoretical models clearly show that the GLT could play a crucial role in these studies.

  13. GRB 081029: A Gamma-Ray Burst with a Multi-Component Afterglow

    Science.gov (United States)

    Holland, Stephen T.; DePasquale, Massimiliano; Mao, Jirong; Sakamoto, Taka; Shady, Patricia; Covino, Stefano; Yi-Zhong, Fan; Zhi-Ping, Jin; D'Avanzo, Paolo; Antonelli, Angelo; hide

    2011-01-01

    We present an analysis of the unusual optical light curve of the gamma-ray burst GRB 081029, a long-soft burst with a redshift of z = 3.8479. We combine X-ray and optical observations from the Swift X-Ray Telescope and the Swift UltraViolet Optical Telescope with ground-based optical and infrared data obtained using the REM and ROTSE telescopes to construct a detailed data set extending from 86 s to approx. 100000 s after the BAT trigger. Our data cover a wide energy range, from 10 keV to 0.77 eV (1.24 A to 16000 A). The X-ray afterglow shows a shallow initial decay followed by a rapid decay starting at about 18000 s. The optical and infrared afterglow, however, shows an uncharacteristic rise at about 5000 s that does not correspond to any feature in the X-ray light curve. Our data are not consistent with synchrotron radiation from a jet interacting with an external medium, a two-component jet, or continuous energy injection from the central engine. We find that the the optical light curves can be broadly explained by a collision between two ejecta shells within a two-component jet. A growing number of gamma-ray burst afterglows are consistent with complex jets, which suggests that some (or all) gamma-ray burst jets are complex and will require detailed modelling to fully understand them.

  14. Magnetars in Ultra-Long Gamma-Ray Bursts and GRB 111209A

    Energy Technology Data Exchange (ETDEWEB)

    Gompertz, B.; Fruchter, A., E-mail: bgompertz@stsci.edu [Space Telescope Science Institute, Baltimore, MD 21218 (United States)

    2017-04-10

    Supernova 2011kl, associated with the ultra-long gamma-ray burst (ULGRB) 111209A, exhibited a higher-than-normal peak luminosity, placing it in the parameter space between regular supernovae and super-luminous supernovae. Its light curve can only be matched by an abnormally high fraction of {sup 56}Ni that appears inconsistent with the observed spectrum, and as a result it has been suggested that the supernova, and by extension the gamma-ray burst, are powered by the spin-down of a highly magnetized millisecond pulsar, known as a magnetar. We investigate the broadband observations of ULGRB 111209A and find two independent measures that suggest a high density circumburst environment. However, the light curve of the GRB afterglow shows no evidence of a jet break (the steep decline that would be expected as the jet slows due to the resistance of the external medium) out to three weeks after trigger, implying a wide jet. Combined with the high isotropic energy of the burst, this implies that only a magnetar with a spin period of ∼1 ms or faster can provide enough energy to power both ULGRB 111209A and Supernova 2011kl.

  15. Method for detecting neutrinos from internal shocks in GRB fireballs with AMANDA

    CERN Document Server

    Stamatikos, M

    2004-01-01

    Neutrino-based astronomy provides a new window on the most energetic processes in the universe. The discovery of high-energy (E >or= 10 /sup 14/ eV) muonic neutrinos (v/sub mu /) from gamma-ray bursts (GRBs) would confirm hadronic acceleration in the relativistic GRB- wind, validate the phenomenology of the canonical fireball model and possibly reveal an acceleration mechanism for the highest energy cosmic rays (CRs). The Antarctic Muon and Neutrino Detector Array (AMANDA) is the world's largest operational neutrino telescope with a PeV muon effective area (averaged over zenith angle) ~ 50,000 m/sup 2 /. AMANDA uses the natural ice at the geographic South Pole as a Cherenkov medium and has been successfully calibrated on the signal of atmospheric neutrinos (v/sub atm/). Contrary to previous diffuse searches, we describe an analysis based upon confronting AMANDA observations of individual GRBs, adequately modeled by fireball phenomenology, with the predictions of the canonical fireball model. The expected neut...

  16. HIGH-ENERGY NON-THERMAL AND THERMAL EMISSION FROM GRB 141207A DETECTED BY FERMI

    Energy Technology Data Exchange (ETDEWEB)

    Arimoto, Makoto [Research Institute for Science and Engineering, Waseda University, 3-4-1, Ohkubo, Shinjuku, Tokyo, 169-8555 (Japan); Asano, Katsuaki [Institute for Cosmic Ray Research, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, 277-8582 (Japan); Ohno, Masanori [Department of Physical Sciences, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima, 739-8526 (Japan); Veres, Péter [Center for Space Plasma and Aeronomic Research (CSPAR), University of Alabama in Huntsville, Huntsville, AL 35899 (United States); Axelsson, Magnus [KTH Royal Institute of Technology, Department of Physics, SE-106 91 Stockholm (Sweden); Bissaldi, Elisabetta [Istituto Nazionale di Fisica Nucleare, Sezione di Bari, I-70126 Bari (Italy); Tachibana, Yutaro; Kawai, Nobuyuki, E-mail: m.arimoto@aoni.waseda.jp [Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 152-8551 (Japan)

    2016-12-20

    A bright long gamma-ray burst GRB 141207A was observed by the Fermi Gamma-ray Space Telescope and detected by both instruments onboard. The observations show that the spectrum in the prompt phase is not well described by the canonical empirical Band function alone, and that an additional power-law component is needed. In the early phase of the prompt emission, a modified blackbody with a hard low-energy photon index ( α  = +0.2 to +0.4) is detected, which suggests a photospheric origin. In a finely time-resolved analysis, the spectra are also well fitted by the modified blackbody combined with a power-law function. We discuss the physical parameters of the photosphere such as the bulk Lorentz factor of the relativistic flow and the radius. We also discuss the physical origin of the extra power-law component observed during the prompt phase in the context of different models such as leptonic and hadronic scenarios in the internal shock regime and synchrotron emission in the external forward shock. In the afterglow phase, the temporal and spectral behaviors of the temporally extended high-energy emission and the fading X-ray emission detected by the X-Ray Telescope on-board Swift are consistent with synchrotron emission in a radiative external forward shock.

  17. A GRB and Broad-lined Type Ic Supernova from a Single Central Engine

    Science.gov (United States)

    Barnes, Jennifer; Duffell, Paul C.; Liu, Yuqian; Modjaz, Maryam; Bianco, Federica B.; Kasen, Daniel; MacFadyen, Andrew I.

    2018-06-01

    Unusually high velocities (≳0.1c) and correspondingly high kinetic energies have been observed in a subset of Type Ic supernovae (so-called “broad-lined Ic” supernovae; SNe Ic-BL), prompting a search for a central engine model capable of generating such energetic explosions. A clue to the explosion mechanism may lie in the fact that all supernovae that accompany long-duration gamma-ray bursts (GRBs) belong to the SN Ic-BL class. Using a combination of two-dimensional relativistic hydrodynamics and radiation transport calculations, we demonstrate that the central engine responsible for long GRBs can also trigger an SN Ic-BL. We find that a reasonable GRB engine injected into a stripped Wolf–Rayet progenitor produces a relativistic jet with energy ∼1051 erg, as well as an SN whose synthetic light curves and spectra are fully consistent with observed SNe Ic-BL during the photospheric phase. As a result of the jet’s asymmetric energy injection, the SN spectra and light curves depend on viewing angle. The impact of viewing angle on the spectrum is particularly pronounced at early times, while the viewing-angle