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Sample records for adaptor molecule grb2

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

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    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.

  2. 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....

  3. 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.

  4. Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc

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    Marks David R

    2009-01-01

    Full Text Available Abstract Background Neurotrophins are important regulators of growth and regeneration, and acutely, they can modulate the activity of voltage-gated ion channels. Previously we have shown that acute brain-derived neurotrophic factor (BDNF activation of neurotrophin receptor tyrosine kinase B (TrkB suppresses the Shaker voltage-gated potassium channel (Kv1.3 via phosphorylation of multiple tyrosine residues in the N and C terminal aspects of the channel protein. It is not known how adaptor proteins, which lack catalytic activity, but interact with members of the neurotrophic signaling pathway, might scaffold with ion channels or modulate channel activity. Results We report the co-localization of two adaptor proteins, neuronal Src homology and collagen (nShc and growth factor receptor-binding protein 10 (Grb10, with Kv1.3 channel as demonstrated through immunocytochemical approaches in the olfactory bulb (OB neural lamina. To further explore the specificity and functional ramification of adaptor/channel co-localization, we performed immunoprecipitation and Western analysis of channel, kinase, and adaptor transfected human embryonic kidney 293 cells (HEK 293. nShc formed a direct protein-protein interaction with Kv1.3 that was independent of BDNF-induced phosphorylation of Kv1.3, whereas Grb10 did not complex with Kv1.3 in HEK 293 cells. Both adaptors, however, co-immunoprecipitated with Kv1.3 in native OB. Grb10 was interestingly able to decrease the total expression of Kv1.3, particularly at the membrane surface, and subsequently eliminated the BDNF-induced phosphorylation of Kv1.3. To examine the possibility that the Src homology 2 (SH2 domains of Grb10 were directly binding to basally phosphorylated tyrosines in Kv1.3, we utilized point mutations to substitute multiple tyrosine residues with phenylalanine. Removal of the tyrosines 111–113 and 449 prevented Grb10 from decreasing Kv1.3 expression. In the absence of either adaptor protein

  5. Tyrosine phosphorylation of Grb14 by Tie2

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    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.

  6. 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...

  7. Expression, refolding and crystallizations of the Grb2-like (GADS) C-terminal SH3 domain complexed with a SLP-76 motif peptide

    International Nuclear Information System (INIS)

    Faravelli, Alessandro; Dimasi, Nazzareno

    2005-01-01

    Several crystals of the Grb2-like C-terminal SH3 domain in complex with a motif peptide from the SLP-76 protein were obtained and characterized. The Grb2-like adaptor protein GADS is composed of an N-terminal SH3 domain, an SH2 domain, a proline-rich region and a C-terminal SH3 domain. GADS interacts through its C-terminal SH3 domain with the adaptor protein SLP-76, thus recruiting this protein and other associated molecules to the linker for activation of T-cell (LAT) protein. The DNA encoding the C-terminal SH3 domain of GADS (GADS-cSH3) was assembled synthetically using a recursive PCR technique and the protein was overexpressed in Escherichia coli, refolded and purified. Several crystals of this domain in complex with the SLP-76 peptide were obtained and characterized

  8. 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.

  9. 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.

  10. 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

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

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    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. 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...

  13. 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

  14. Caenorhabditis elegans fibroblast growth factor receptor signaling can occur independently of the multi-substrate adaptor FRS2.

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    Lo, Te-Wen; Bennett, Daniel C; Goodman, S Jay; Stern, Michael J

    2010-06-01

    The components of receptor tyrosine kinase signaling complexes help to define the specificity of the effects of their activation. The Caenorhabditis elegans fibroblast growth factor receptor (FGFR), EGL-15, regulates a number of processes, including sex myoblast (SM) migration guidance and fluid homeostasis, both of which require a Grb2/Sos/Ras cassette of signaling components. Here we show that SEM-5/Grb2 can bind directly to EGL-15 to mediate SM chemoattraction. A yeast two-hybrid screen identified SEM-5 as able to interact with the carboxy-terminal domain (CTD) of EGL-15, a domain that is specifically required for SM chemoattraction. This interaction requires the SEM-5 SH2-binding motifs present in the CTD (Y(1009) and Y(1087)), and these sites are required for the CTD role of EGL-15 in SM chemoattraction. SEM-5, but not the SEM-5 binding sites located in the CTD, is required for the fluid homeostasis function of EGL-15, indicating that SEM-5 can link to EGL-15 through an alternative mechanism. The multi-substrate adaptor protein FRS2 serves to link vertebrate FGFRs to Grb2. In C. elegans, an FRS2-like gene, rog-1, functions upstream of a Ras/MAPK pathway for oocyte maturation but is not required for EGL-15 function. Thus, unlike the vertebrate FGFRs, which require the multi-substrate adaptor FRS2 to recruit Grb2, EGL-15 can recruit SEM-5/Grb2 directly.

  15. 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...

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

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    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.

  17. Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins*

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    Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

    2017-01-01

    Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. PMID:27927989

  18. Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins.

    Science.gov (United States)

    Inaba, Satomi; Numoto, Nobutaka; Ogawa, Shuhei; Morii, Hisayuki; Ikura, Teikichi; Abe, Ryo; Ito, Nobutoshi; Oda, Masayuki

    2017-01-20

    Full activation of T cells and differentiation into effector T cells are essential for many immune responses and require co-stimulatory signaling via the CD28 receptor. Extracellular ligand binding to CD28 recruits protein-tyrosine kinases to its cytoplasmic tail, which contains a YMNM motif. Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity, and all are important for CD28-mediated co-stimulatory function. However, the mechanism of how these proteins recognize and compete for CD28 is unclear. To visualize their interactions with CD28, we have determined the crystal structures of Gads SH2 and two p85 SH2 domains in complex with a CD28-derived phosphopeptide. The high resolution structures obtained revealed that, whereas the CD28 phosphopeptide bound to Gads SH2 is in a bent conformation similar to that when bound to Grb2 SH2, it adopts a more extended conformation when bound to the N- and C-terminal SH2 domains of p85. These differences observed in the peptide-protein interactions correlated well with the affinity and other thermodynamic parameters for each interaction determined by isothermal titration calorimetry. The detailed insight into these interactions reported here may inform the development of compounds that specifically inhibit the association of CD28 with these adaptor proteins to suppress excessive T cell responses, such as in allergies and autoimmune diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. 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

  20. Binding of the cSH3 domain of Grb2 adaptor to two distinct RXXK motifs within Gab1 docker employs differential mechanisms.

    Science.gov (United States)

    McDonald, Caleb B; Seldeen, Kenneth L; Deegan, Brian J; Bhat, Vikas; Farooq, Amjad

    2011-01-01

    A ubiquitous component of cellular signaling machinery, Gab1 docker plays a pivotal role in routing extracellular information in the form of growth factors and cytokines to downstream targets such as transcription factors within the nucleus. Here, using isothermal titration calorimetry (ITC) in combination with macromolecular modeling (MM), we show that although Gab1 contains four distinct RXXK motifs, designated G1, G2, G3, and G4, only G1 and G2 motifs bind to the cSH3 domain of Grb2 adaptor and do so with distinct mechanisms. Thus, while the G1 motif strictly requires the PPRPPKP consensus sequence for high-affinity binding to the cSH3 domain, the G2 motif displays preference for the PXVXRXLKPXR consensus. Such sequential differences in the binding of G1 and G2 motifs arise from their ability to adopt distinct polyproline type II (PPII)- and 3(10) -helical conformations upon binding to the cSH3 domain, respectively. Collectively, our study provides detailed biophysical insights into a key protein-protein interaction involved in a diverse array of signaling cascades central to health and disease. Copyright © 2010 John Wiley & Sons, Ltd.

  1. 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...

  2. 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.

  3. APS, an adaptor molecule containing PH and SH2 domains, has a negative regulatory role in B cell proliferation

    International Nuclear Information System (INIS)

    Iseki, Masanori; Kubo-Akashi, Chiyomi; Kwon, Sang-Mo; Yamaguchi, Akiko; Takatsu, Kiyoshi; Takaki, Satoshi

    2005-01-01

    Adaptor molecule containing PH and SH2 domains (APS) is an intracellular adaptor protein that forms part of an adaptor family along with Lnk and SH2-B. APS transcripts are expressed in various tissues including brain, kidney, and muscle, as well as in splenic B cells but not in T cells. We investigated the functions of APS in B cell development and activation by generating APS-transgenic (APS-Tg) mice that overexpressed APS in lymphocytes. The number of B-1 cells in the peritoneal cavity was reduced in APS-Tg mice, as were B-2 cells in the spleen. B cell development in the bone marrow was partially impaired at the transition stage from proliferating large pre-B to small pre-B cells. B cell proliferation induced by B cell receptor (BCR) crosslinking but not by other B cell mitogens was also impaired in APS-Tg mice. APS co-localized with BCR complexes and filamentous actin in activated APS-Tg B cells. Thus, APS appears to play novel negative regulatory roles in BCR signaling, actin reorganization pathways, and control of compartment sizes of B-lineage cells

  4. 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

  5. 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

  6. Structural and biophysical investigation of the interaction of a mutant Grb2 SH2 domain (W121G) with its cognate phosphopeptide.

    Science.gov (United States)

    Papaioannou, Danai; Geibel, Sebastian; Kunze, Micha B A; Kay, Christopher W M; Waksman, Gabriel

    2016-03-01

    The adaptor protein Grb2 is a key element of mitogenetically important signaling pathways. With its SH2 domain it binds to upstream targets while its SH3 domains bind to downstream proteins thereby relaying signals from the cell membranes to the nucleus. The Grb2 SH2 domain binds to its targets by recognizing a phosphotyrosine (pY) in a pYxNx peptide motif, requiring an Asn at the +2 position C-terminal to the pY with the residue either side of this Asn being hydrophobic. Structural analysis of the Grb2 SH2 domain in complex with its cognate peptide has shown that the peptide adopts a unique β-turn conformation, unlike the extended conformation that phosphopeptides adopt when bound to other SH2 domains. TrpEF1 (W121) is believed to force the peptide into this unusual conformation conferring this unique specificity to the Grb2 SH2 domain. Using X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and isothermal titration calorimetry (ITC), we describe here a series of experiments that explore the role of TrpEF1 in determining the specificity of the Grb2 SH2 domain. Our results demonstrate that the ligand does not adopt a pre-organized structure before binding to the SH2 domain, rather it is the interaction between the two that imposes the hairpin loop to the peptide. Furthermore, we find that the peptide adopts a similar structure when bound to both the wild-type Grb2 SH2 domain and a TrpEF1Gly mutant. This suggests that TrpEF1 is not the determining factor for the conformation of the phosphopeptide. © 2015 The Protein Society.

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

    Science.gov (United States)

    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.

  8. 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...

  9. Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway.

    Science.gov (United States)

    Tauchi, T; Boswell, H S; Leibowitz, D; Broxmeyer, H E

    1994-01-01

    Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)-dependent hematopoietic cell lines to growth factor-independent proliferation. It has been demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras pathway to exert their transforming effect. In particular, p210bcr-abl was recently found to effect p21ras activation in hematopoietic cells. In this context, experiments were performed to evaluate a protein signaling pathway by which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a protein containing a src-homology region 2 (SH2) domain, and known to function upstream from p21ras, might form specific complexes with p210bcr-abl and thus, possibly alter p21ras activity by coupling to the guanine nucleotide exchange factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has been previously demonstrated to occur ubiquitously. We found that p210bcr-abl formed a specific complex with Shc and with Grb2 in three different murine cell lines transfected with a p210bcr-abl expression vector. There appeared to be a higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to p210bcr-abl transformed cells, in which there was constitutive tight association between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)-dependent in a SLF-responsive, nontransformed parental cell line. The SLF-dependent association between Grb2 and Shc in nontransformed cells involved formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus, p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to allow growth factor-independent coupling between Grb2, which exists in a complex with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.

  10. SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1.

    Science.gov (United States)

    Anafi, M; Kiefer, F; Gish, G D; Mbamalu, G; Iscove, N N; Pawson, T

    1997-10-31

    Ste20-related protein kinases have been implicated as regulating a range of cellular responses, including stress-activated protein kinase pathways and the control of cytoskeletal architecture. An important issue involves the identities of the upstream signals and regulators that might control the biological functions of mammalian Ste20-related protein kinases. HPK1 is a protein-serine/threonine kinase that possesses a Ste20-like kinase domain, and in transfected cells activates a protein kinase pathway leading to the stress-activated protein kinase SAPK/JNK. Here we have investigated candidate upstream regulators that might interact with HPK1. HPK1 possesses an N-terminal catalytic domain and an extended C-terminal tail with four proline-rich motifs. The SH3 domains of Grb2 bound in vitro to specific proline-rich motifs in the HPK1 tail and functioned synergistically to direct the stable binding of Grb2 to HPK1 in transfected Cos1 cells. Epidermal growth factor (EGF) stimulation did not affect the binding of Grb2 to HPK1 but induced recruitment of the Grb2.HPK1 complex to the autophosphorylated EGF receptor and to the Shc docking protein. Several activated receptor and cytoplasmic tyrosine kinases, including the EGF receptor, stimulated the tyrosine phosphorylation of the HPK1 serine/threonine kinase. These results suggest that HPK1, a mammalian Ste20-related protein-serine/threonine kinase, can potentially associate with protein-tyrosine kinases through interactions mediated by SH2/SH3 adaptors such as Grb2. Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases.

  11. Expression of the Grb2-related protein of the lymphoid system in B cell subsets enhances B cell antigen receptor signaling through mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Yankee, Thomas M; Solow, Sasha A; Draves, Kevin D; Clark, Edward A

    2003-01-01

    Adapter proteins play a critical role in regulating signals triggered by Ag receptor cross-linking. These small molecules link receptor proximal events with downstream signaling pathways. In this study, we explore the expression and function of the Grb2-related protein of the lymphoid system (GrpL)/Grb2-related adaptor downstream of Shc adapter protein in human B cells. GrpL is expressed in naive B cells and is down-regulated following B cell Ag receptor ligation. By contrast, germinal center and memory B cells express little or no GrpL. Using human B cell lines, we detected constitutive interactions between GrpL and B cell linker protein, Src homology (SH)2 domain-containing leukocyte protein of 76 kDa, hemopoietic progenitor kinase 1, and c-Cbl. The N-terminal SH3 domain of GrpL binds c-Cbl while the C-terminal SH3 domain binds B cell linker protein and SH2 domain-containing leukocyte protein of 76 kDa. Exogenous expression of GrpL in a GrpL-negative B cell line leads to enhanced Ag receptor-induced extracellular signal-related kinase and p38 mitogen-activated protein kinase phosphorylation. Thus, GrpL expression in human B cell subsets appears to regulate Ag receptor-mediated signaling events.

  12. 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.

  13. 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.

  14. 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...

  15. 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

  16. Disabled is a putative adaptor protein that functions during signaling by the sevenless receptor tyrosine kinase.

    Science.gov (United States)

    Le, N; Simon, M A

    1998-08-01

    DRK, the Drosophila homolog of the SH2-SH3 domain adaptor protein Grb2, is required during signaling by the sevenless receptor tyrosine kinase (SEV). One role of DRK is to provide a link between activated SEV and the Ras1 activator SOS. We have investigated the possibility that DRK performs other functions by identifying additional DRK-binding proteins. We show that the phosphotyrosine-binding (PTB) domain-containing protein Disabled (DAB) binds to the DRK SH3 domains. DAB is expressed in the ommatidial clusters, and loss of DAB function disrupts ommatidial development. Moreover, reduction of DAB function attenuates signaling by a constitutively activated SEV. Our biochemical analysis suggests that DAB binds SEV directly via its PTB domain, becomes tyrosine phosphorylated upon SEV activation, and then serves as an adaptor protein for SH2 domain-containing proteins. Taken together, these results indicate that DAB is a novel component of the SEV signaling pathway.

  17. 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.

  18. 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.

  19. 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

  20. Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.

    Science.gov (United States)

    Roskoski, Robert

    2005-11-11

    Signaling by stem cell factor and Kit, its receptor, plays important roles in gametogenesis, hematopoiesis, mast cell development and function, and melanogenesis. Moreover, human and mouse embryonic stem cells express Kit transcripts. Stem cell factor exists as both a soluble and a membrane-bound glycoprotein while Kit is a receptor protein-tyrosine kinase. The complete absence of stem cell factor or Kit is lethal. Deficiencies of either produce defects in red and white blood cell production, hypopigmentation, and sterility. Gain-of-function mutations of Kit are associated with several human neoplasms including acute myelogenous leukemia, gastrointestinal stromal tumors, and mastocytomas. Kit consists of an extracellular domain, a transmembrane segment, a juxtamembrane segment, and a protein kinase domain that contains an insert of about 80 amino acid residues. Binding of stem cell factor to Kit results in receptor dimerization and activation of protein kinase activity. The activated receptor becomes autophosphorylated at tyrosine residues that serve as docking sites for signal transduction molecules containing SH2 domains. The adaptor protein APS, Src family kinases, and Shp2 tyrosyl phosphatase bind to phosphotyrosine 568. Shp1 tyrosyl phosphatase and the adaptor protein Shc bind to phosphotyrosine 570. C-terminal Src kinase homologous kinase and the adaptor Shc bind to both phosphotyrosines 568 and 570. These residues occur in the juxtamembrane segment of Kit. Three residues in the kinase insert domain are phosphorylated and attract the adaptor protein Grb2 (Tyr703), phosphatidylinositol 3-kinase (Tyr721), and phospholipase Cgamma (Tyr730). Phosphotyrosine 900 in the distal kinase domain binds phosphatidylinositol 3-kinase which in turn binds the adaptor protein Crk. Phosphotyrosine 936, also in the distal kinase domain, binds the adaptor proteins APS, Grb2, and Grb7. Kit has the potential to participate in multiple signal transduction pathways as a result of

  1. 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...

  2. One-way membrane trafficking of SOS in receptor-triggered Ras activation.

    Science.gov (United States)

    Christensen, Sune M; Tu, Hsiung-Lin; Jun, Jesse E; Alvarez, Steven; Triplet, Meredith G; Iwig, Jeffrey S; Yadav, Kamlesh K; Bar-Sagi, Dafna; Roose, Jeroen P; Groves, Jay T

    2016-09-01

    SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted-membrane experiments, these Grb2-independent interactions were sufficient to retain human SOS on the membrane for many minutes, during which a single SOS molecule could processively activate thousands of Ras molecules. These observations raised questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative assays of reconstituted SOS-deficient chicken B-cell signaling systems combined with single-molecule measurements in supported membranes. These studies revealed an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until being actively removed via endocytosis.

  3. 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.

  4. The adaptor molecule Nck localizes the WAVE complex to promote actin polymerization during CEACAM3-mediated phagocytosis of bacteria.

    Directory of Open Access Journals (Sweden)

    Stefan Pils

    Full Text Available BACKGROUND: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. PRINCIPAL FINDINGS: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. CONCLUSIONS: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.

  5. Transmembrane adaptor molecules: a new category of lymphoid-cell markers

    Czech Academy of Sciences Publication Activity Database

    Tedoldi, S.; Paterson, J.C.; Hansmann, M.-L.; Natkunam, Y.; Rüdiger, T.; Angelisová, Pavla; Du, M.Q.; Roberton, H.; Roncador, G.; Sanchez, L.; Pozzobon, M.; Masir, N.; Barry, R.; Pileri, S.; Mason, D.Y.; Marafioti, T.; Hořejší, Václav

    2006-01-01

    Roč. 107, č. 1 (2006), s. 213-221 ISSN 0006-4971 R&D Projects: GA MŠk(CZ) 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : transmembrane adaptors * PAG * LIME Subject RIV: EC - Immunology Impact factor: 10.370, year: 2006

  6. 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.

  7. 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.

  8. Association between GRB2/Sos and insulin receptor substrate 1 is not sufficient for activation of extracellular signal-regulated kinases by interleukin-4: implications for Ras activation by insulin.

    Science.gov (United States)

    Pruett, W; Yuan, Y; Rose, E; Batzer, A G; Harada, N; Skolnik, E Y

    1995-03-01

    Insulin receptor substrate 1 (IRS-1) mediates the activation of a variety of signaling pathways by the insulin and insulin-like growth factor 1 receptors by serving as a docking protein for signaling molecules with SH2 domains. We and others have shown that in response to insulin stimulation IRS-1 binds GRB2/Sos and have proposed that this interaction is important in mediating Ras activation by the insulin receptor. Recently, it has been shown that the interleukin (IL)-4 receptor also phosphorylates IRS-1 and an IRS-1-related molecule, 4PS. Unlike insulin, however, IL-4 fails to activate Ras, extracellular signal-regulated kinases (ERKs), or mitogen-activated protein kinases. We have reconstituted the IL-4 receptor into an insulin-responsive L6 myoblast cell line and have shown that IRS-1 is tyrosine phosphorylated to similar degrees in response to insulin and IL-4 stimulation in this cell line. In agreement with previous findings, IL-4 failed to activate the ERKs in this cell line or to stimulate DNA synthesis, whereas the same responses were activated by insulin. Surprisingly, IL-4's failure to activate ERKs was not due to a failure to stimulate the association of tyrosine-phosphorylated IRS-1 with GRB2/Sos; the amounts of GRB2/Sos associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. Moreover, the amounts of phosphatidylinositol 3-kinase activity associated with IRS-1 were similar in insulin- and IL-4-stimulated cells. In contrast to insulin, however, IL-4 failed to induce tyrosine phosphorylation of Shc or association of Shc with GRB2. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Thus, ERK activation correlates with Shc tyrosine phosphorylation and formation of an Shc/GRB2 complex. Previous studies have indicated that activation of ERks in this cell line is dependent upon Ras since a dominant-negative Ras (Asn-17) blocks ERK activation by insulin. Our findings, taken in the context

  9. 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

  10. 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.

  11. 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...

  12. 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...

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression.

    Science.gov (United States)

    Patsoukis, Nikolaos; Bardhan, Kankana; Weaver, Jessica D; Sari, Duygu; Torres-Gomez, Alvaro; Li, Lequn; Strauss, Laura; Lafuente, Esther M; Boussiotis, Vassiliki A

    2017-08-22

    Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules. Through its various domains, RIAM is a critical node of signal integration for activation of T cells, recruits monomeric and polymerized actin to drive actin remodeling and cytoskeletal reorganization, and promotes inside-out integrin signaling in T cells. As a regulator of inside-out integrin activation, RIAM affects multiple functions of innate and adaptive immunity. The effects of RIAM on cytoskeletal reorganization and integrin activation have implications in cell migration and trafficking of cancer cells. We provide an overview of the structure and interactions of RIAM, and we discuss the implications of RIAM functions in innate and adaptive immunity and cancer. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. The adaptor molecule SAP plays essential roles during invariant NKT cell cytotoxicity and lytic synapse formation.

    Science.gov (United States)

    Das, Rupali; Bassiri, Hamid; Guan, Peng; Wiener, Susan; Banerjee, Pinaki P; Zhong, Ming-Chao; Veillette, André; Orange, Jordan S; Nichols, Kim E

    2013-04-25

    The adaptor molecule signaling lymphocytic activation molecule-associated protein (SAP) plays critical roles during invariant natural killer T (iNKT) cell ontogeny. As a result, SAP-deficient humans and mice lack iNKT cells. The strict developmental requirement for SAP has made it difficult to discern its possible involvement in mature iNKT cell functions. By using temporal Cre recombinase-mediated gene deletion to ablate SAP expression after completion of iNKT cell development, we demonstrate that SAP is essential for T-cell receptor (TCR)-induced iNKT cell cytotoxicity against T-cell and B-cell leukemia targets in vitro and iNKT-cell-mediated control of T-cell leukemia growth in vivo. These findings are not restricted to the murine system: silencing RNA-mediated suppression of SAP expression in human iNKT cells also significantly impairs TCR-induced cytolysis. Mechanistic studies reveal that iNKT cell killing requires the tyrosine kinase Fyn, a known SAP-binding protein. Furthermore, SAP expression is required within iNKT cells to facilitate their interaction with T-cell targets and induce reorientation of the microtubule-organizing center to the immunologic synapse (IS). Collectively, these studies highlight a novel and essential role for SAP during iNKT cell cytotoxicity and formation of a functional IS.

  4. Adaptor proteins intersectin 1 and 2 bind similar proline-rich ligands but are differentially recognized by SH2 domain-containing proteins.

    Directory of Open Access Journals (Sweden)

    Olga Novokhatska

    Full Text Available BACKGROUND: Scaffolding proteins of the intersectin (ITSN family, ITSN1 and ITSN2, are crucial for the initiation stage of clathrin-mediated endocytosis. These proteins are closely related but have implications in distinct pathologies. To determine how these proteins could be separated in certain cell pathways we performed a comparative study of ITSNs. METHODOLOGY/PRINCIPAL FINDINGS: We have shown that endogenous ITSN1 and ITSN2 colocalize and form a complex in cells. A structural comparison of five SH3 domains, which mediated most ITSNs protein-protein interactions, demonstrated a similarity of their ligand-binding sites. We showed that the SH3 domains of ITSN2 bound well-established interactors of ITSN1 as well as newly identified ITSNs protein partners. A search for a novel interacting interface revealed multiple tyrosines that could be phosphorylated in ITSN2. Phosphorylation of ITSN2 isoforms but not ITSN1 short isoform was observed in various cell lines. EGF stimulation of HeLa cells enhanced tyrosine phosphorylation of ITSN2 isoforms and enabled their recognition by the SH2 domains of the Fyn, Fgr and Abl1 kinases, the regulatory subunit of PI3K, the adaptor proteins Grb2 and Crk, and phospholipase C gamma. The SH2 domains mentioned were unable to bind ITSN1 short isoform. CONCLUSIONS/SIGNIFICANCE: Our results indicate that during evolution of vertebrates ITSN2 acquired a novel protein-interaction interface that allows its specific recognition by the SH2 domains of signaling proteins. We propose that these data could be important to understand the functional diversity of paralogous ITSN proteins.

  5. Regulation of ITAM adaptor molecules and their receptors by inhibition of calcineurin-NFAT signalling during late stage osteoclast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Zawawi, M.S.F. [Universiti Sains Malaysia (USM) (Malaysia); Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia); Dharmapatni, A.A.S.S.K.; Cantley, M.D. [Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia); McHugh, K.P. [University of Florida, College of Dentistry, Fl (United States); Haynes, D.R. [Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia); Crotti, T.N., E-mail: tania.crotti@adelaide.edu.au [Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Calcineurin/NFAT inhibitors FK506 and VIVIT treated human PBMC derived osteoclasts in vitro. Black-Right-Pointing-Pointer Differential regulation of ITAM receptors and adaptor molecules by calcineurin/NFAT inhibitors. Black-Right-Pointing-Pointer FK506 and VIVIT suppress ITAM factors during late phase osteoclast differentiation. -- Abstract: Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcR{gamma}) and DNAX-activating protein 12 kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin ({beta}3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10 days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real

  6. U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo

    Directory of Open Access Journals (Sweden)

    Rafal Goraczniak

    2013-01-01

    Full Text Available U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2 and metabotropic glutamate receptor 1 (GRM1, in a human melanoma cell xenograft mouse model system. Using a newly developed dendrimer delivery system, anti-BCL2 U1 Adaptors were very potent and suppressed tumor growth at doses as low as 34 µg/kg with twice weekly intravenous (iv administration. Anti-GRM1 U1 Adaptors suppressed tumor xenograft growth with similar potency. Mechanism of action was demonstrated by showing target gene suppression in tumors and by observing that negative control U1 Adaptors with just one functional domain show no tumor suppression activity. The anti-BCL2 and anti-GRM1 treatments were equally effective against cell lines harboring either wild-type or a mutant V600E B-RAF allele, the most common mutation in melanoma. Treatment of normal immune-competent mice (C57BL6 indicated no organ toxicity or immune stimulation. These proof-of-concept studies represent an in-depth (over 800 mice in ~108 treatment groups validation that U1 Adaptors are a highly potent gene-silencing therapeutic and open the way for their further development to treat other human diseases.

  7. Activation of the JNK pathway is essential for transformation by the Met oncogene.

    Science.gov (United States)

    Rodrigues, G A; Park, M; Schlessinger, J

    1997-05-15

    The Met/Hepatocyte Growth Factor (HGF) receptor tyrosine kinase is oncogenically activated through a rearrangement that creates a hybrid gene Tpr-Met. The resultant chimeric p65(Tpr-Met) protein is constitutively phosphorylated on tyrosine residues in vivo and associates with a number of SH2-containing signaling molecules including the p85 subunit of PI-3 kinase and the Grb2 adaptor protein, which couples receptor tyrosine kinases to the Ras signaling pathway. Mutation of the binding site for Grb2 impairs the ability of Tpr-Met oncoprotein to transform fibroblasts, suggesting that the activation of the Ras/MAP kinase signaling pathway through Grb2 may be essential for cellular transformation. To test this hypothesis dominant-negative mutants of Grb2 with deletions of the SH3 domains were introduced into Tpr-Met transformed fibroblasts. Cells overexpressing the mutants were found to be morphologically reverted and exhibited reduced growth in soft agar. Surprisingly, the Grb2 mutants blocked activation of the JNK/SAPK but not MAP kinase activity induced by the Tpr-Met oncoprotein. Additionally, cells expressing dominant-negative Grb2 mutants had reduced PI-3-kinase activity and dominant-negative mutants of Rac1 blocked both Tpr-Met-induced transformation and activation of JNK. These experiments reveal a novel link between Met and the JNK pathway, which is essential for transformation by this oncogene.

  8. The adaptor Lnk (SH2B3): an emerging regulator in vascular cells and a link between immune and inflammatory signaling.

    Science.gov (United States)

    Devallière, Julie; Charreau, Béatrice

    2011-11-15

    A better knowledge of the process by which inflammatory extracellular signals are relayed from the plasma membrane to specific intracellular sites is a key step to understand how inflammation develops and how it is regulated. This review focuses on Lnk (SH2B3) a member, with SH2B1 and SH2B2, of the SH2B family of adaptor proteins that influences a variety of signaling pathways mediated by Janus kinase and receptor tyrosine kinases. SH2B adaptor proteins contain conserved dimerization, pleckstrin homology, and SH2 domains. Initially described as a regulator of hematopoiesis and lymphocyte differentiation, Lnk now emerges as a key regulator in hematopoeitic and non hematopoeitic cells such as endothelial cells (EC) moderating growth factor and cytokine receptor-mediated signaling. In EC, Lnk is a negative regulator of TNF signaling that reduce proinflammatory phenotype and prevent EC from apoptosis. Lnk is a modulator in integrin signaling and actin cytoskeleton organization in both platelets and EC with an impact on cell adhesion, migration and thrombosis. In this review, we discuss some recent insights proposing Lnk as a key regulator of bone marrow-endothelial progenitor cell kinetics, including the ability to cell growth, endothelial commitment, mobilization, and recruitment for vascular regeneration. Finally, novel findings also provided evidences that mutations in Lnk gene are strongly linked to myeloproliferative disorders but also autoimmune and inflammatory syndromes where both immune and vascular cells display a role. Overall, these studies emphasize the importance of the Lnk adaptor molecule not only as prognostic marker but also as potential therapeutic target. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. 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

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Adaptor assembly for coupling turbine blades to rotor disks

    Science.gov (United States)

    Garcia-Crespo, Andres Jose; Delvaux, John McConnell

    2014-09-23

    An adaptor assembly for coupling a blade root of a turbine blade to a root slot of a rotor disk is described. The adaptor assembly includes a turbine blade having a blade root and an adaptor body having an adaptor root. The adaptor body defines a slot having an open end configured to receive the blade root of the turbine blade such that the adaptor root of the adaptor body and the blade root of the turbine blade are adjacent to one another when the blade root of the turbine blade is positioned within the slot. Both the adaptor root of the adaptor body and the blade root of the turbine blade are configured to be received within the root slot of the rotor disk.

  17. 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.

  18. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1.

    Science.gov (United States)

    Rozakis-Adcock, M; Fernley, R; Wade, J; Pawson, T; Bowtell, D

    1993-05-06

    Many tyrosine kinases, including the receptors for hormones such as epidermal growth factor (EGF), nerve growth factor and insulin, transmit intracellular signals through Ras proteins. Ligand binding to such receptors stimulates Ras guanine-nucleotide-exchange activity and increases the level of GTP-bound Ras, suggesting that these tyrosine kinases may activate a guanine-nucleotide releasing protein (GNRP). In Caenorhabditis elegans and Drosophila, genetic studies have shown that Ras activation by tyrosine kinases requires the protein Sem-5/drk, which contains a single Src-homology (SH) 2 domain and two flanking SH3 domains. Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through its SH2 domain. Here we show that in rodent fibroblasts, the SH3 domains of Grb2 are bound to the proline-rich carboxy-terminal tail of mSos1, a protein homologous to Drosophila Sos. Sos is required for Ras signalling and contains a central domain related to known Ras-GNRPs. EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras-GNRP in mammalian cells.

  19. 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

  20. 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...

  1. 21 CFR 870.3620 - Pacemaker lead adaptor.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a pacemaker lead so that it...

  2. 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.

  3. Synthetic protein scaffolds based on peptide motifs and cognate adaptor domains for improving metabolic productivity

    Directory of Open Access Journals (Sweden)

    Anselm H.C. Horn

    2015-11-01

    Full Text Available The efficiency of many cellular processes relies on the defined interaction among different proteins within the same metabolic or signaling pathway. Consequently, a spatial colocalization of functionally interacting proteins has frequently emerged during evolution. This concept has been adapted within the synthetic biology community for the purpose of creating artificial scaffolds. A recent advancement of this concept is the use of peptide motifs and their cognate adaptor domains. SH2, SH3, GBD, and PDZ domains have been used most often in research studies to date. The approach has been successfully applied to the synthesis of a variety of target molecules including catechin, D-glucaric acid, H2, hydrochinone, resveratrol, butyrate, gamma-aminobutyric acid, and mevalonate. Increased production levels of up to 77-fold have been observed compared to non-scaffolded systems. A recent extension of this concept is the creation of a covalent linkage between peptide motifs and adaptor domains, which leads to a more stable association of the scaffolded systems and thus bears the potential to further enhance metabolic productivity.

  4. 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.

  5. 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.

  6. Interactions between the Hepatitis C Virus Nonstructural 2 Protein and Host Adaptor Proteins 1 and 4 Orchestrate Virus Release

    Directory of Open Access Journals (Sweden)

    Fei Xiao

    2018-03-01

    Full Text Available Hepatitis C virus (HCV spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly. We demonstrated that the host kinases AAK1 and GAK regulate HCV infection by controlling these clathrin-associated APs. Here, we sought to define the roles of AP-4, a clathrin-independent adaptor; AP-1A; and AP-1B in HCV infection. We screened for interactions between HCV proteins and the μ subunits of AP-1A, AP-1B, and AP-4 by mammalian cell-based protein fragment complementation assays. The nonstructural 2 (NS2 protein emerged as an interactor of these adaptors in this screening and by coimmunoprecipitations in HCV-infected cells. Two previously unrecognized dileucine-based motifs in the NS2 C terminus mediated AP binding and HCV release. Infectivity and coculture assays demonstrated that while all three adaptors mediate HCV release and cell-free spread, AP-1B and AP-4, but not AP-1A, mediate cell-to-cell spread. Live-cell imaging revealed HCV cotrafficking with AP-1A, AP-1B, and AP-4 and that AP-4 mediates HCV trafficking in a post-Golgi compartment. Lastly, HCV cell-to-cell spread was regulated by AAK1 and GAK and thus susceptible to treatment with AAK1 and GAK inhibitors. These data provide a mechanistic understanding of HCV trafficking in distinct release pathways and reveal a requirement for APs in cell-to-cell viral spread.

  7. 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

  8. Preparation and crystallization of the Grb7 SH2 domain in complex with the G7-18NATE nonphosphorylated cyclic inhibitor peptide

    International Nuclear Information System (INIS)

    Yap, Min Y.; Wilce, Matthew C. J.; Clayton, Daniel J.; Perlmutter, Patrick; Aguilar, Marie-Isabel; Wilce, Jacqueline A.

    2010-01-01

    The preparation and successful crystallization of the Grb7 SH2 domain in complex with the specific cyclic peptide inhibitor G7-18NATE are reported. This structure is anticipated to reveal the basis of the binding affinity and specificity and to assist with the development of second-generation inhibitors of Grb7, which is involved in cancer progression. Grb7 is an adapter protein that is involved in signalling pathways that mediate eukaryotic cell proliferation and migration. Its overexpression in several cancer types has implicated it in cancer progression and led to the development of the G7-18NATE cyclic peptide inhibitor. Here, the preparation of crystals of G7-18NATE in complex with its Grb7 SH2 domain target is reported. Crystals of the complex were grown by the hanging-drop vapour-diffusion method using PEG 3350 as the precipitant at room temperature. X-ray diffraction data were collected from crystals to 2.4 Å resolution using synchrotron X-ray radiation at 100 K. The diffraction was consistent with space group P2 1 , with unit-cell parameters a = 52.7, b = 79.1, c = 54.7 Å, α = γ = 90.0, β = 104.4°. The structure of the G7-18NATE peptide in complex with its target will facilitate the rational development of Grb7-targeted cancer therapeutics

  9. New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Ebbe Toftgaard Poulsen

    2015-12-01

    Full Text Available The Amyloid Precursor Protein (APP has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ in Alzheimer’s disease (AD. However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y682 mutation in the 682YENPTY687 domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS on hippocampal tissue extracts of three month-old mice incubated with either the 682YENPTY687 peptide, its mutated form, 682GENPTY687 or its phosphorylated form, 682pYENPTY687. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc and its Adaptor Protein 2 (AP-2. Overall our results consolidate and refine the importance of Y682 in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies.

  10. 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.

  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. 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...

  13. 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....

  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. 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)

  16. 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

  17. p130Cas scaffolds the signalosome to direct adaptor-effector cross talk during Kaposi's sarcoma-associated herpesvirus trafficking in human microvascular dermal endothelial cells.

    Science.gov (United States)

    Bandyopadhyay, Chirosree; Veettil, Mohanan Valiya; Dutta, Sujoy; Chandran, Bala

    2014-12-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with cell surface receptors, such as heparan sulfate, integrins (α3β1, αVβ3, and αVβ5), and EphrinA2 (EphA2), and activates focal adhesion kinase (FAK), Src, phosphoinositol 3-kinase (PI3-K), c-Cbl, and RhoA GTPase signal molecules early during lipid raft (LR)-dependent productive macropinocytic entry into human dermal microvascular endothelial cells. Our recent studies have identified CIB1 as a signal amplifier facilitating EphA2 phosphorylation and subsequent cytoskeletal cross talk during KSHV macropinocytosis. Although CIB1 lacks an enzymatic activity and traditional adaptor domain or known interacting sequence, it associated with the KSHV entry signal complex and the CIB1-KSHV association was sustained over 30 min postinfection. To identify factors scaffolding the EphA2-CIB1 signal axis, the role of major cellular scaffold protein p130Cas (Crk-associated substrate of Src) was investigated. Inhibitor and small interfering RNA (siRNA) studies demonstrated that KSHV induced p130Cas in an EphA2-, CIB1-, and Src-dependent manner. p130Cas and Crk were associated with KSHV, LRs, EphA2, and CIB1 early during infection. Live-cell microscopy and biochemical studies demonstrated that p130Cas knockdown did not affect KSHV entry but significantly reduced productive nuclear trafficking of viral DNA and routed KSHV to lysosomal degradation. p130Cas aided in scaffolding adaptor Crk to downstream guanine nucleotide exchange factor phospho-C3G possibly to coordinate GTPase signaling during KSHV trafficking. Collectively, these studies demonstrate that p130Cas acts as a bridging molecule between the KSHV-induced entry signal complex and the downstream trafficking signalosome in endothelial cells and suggest that simultaneous targeting of KSHV entry receptors with p130Cas would be an attractive potential avenue for therapeutic intervention in KSHV infection. Eukaryotic cell adaptor molecules, without any intrinsic

  18. 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

  19. Styles of Creativity: Adaptors and Innovators in a Singapore Context

    Science.gov (United States)

    Ee, Jessie; Seng, Tan Oon; Kwang, Ng Aik

    2007-01-01

    Kirton (1976) described two creative styles, namely adaptors and innovators. Adaptors prefer to "do things better" whilst, innovators prefer to "do things differently". This study explored the relationship between two creative styles (adaptor and innovator) and the Big Five personality traits (extraversion, agreeableness, conscientiousness,…

  20. Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

    Science.gov (United States)

    Chen, Buxin; Dores, Michael R.; Grimsey, Neil; Canto, Isabel; Barker, Breann L.; Trejo, JoAnn

    2011-01-01

    Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs. PMID:21965661

  1. 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.

  2. 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)

  3. 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).

  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. 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.

  6. Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes

    Czech Academy of Sciences Publication Activity Database

    Stork, B.; Engelke, M.; Frey, J.; Hořejší, Václav; Hamm-Baarke, A.; Schraven, B.; Kurosaki, T.; Wienands, J.

    2004-01-01

    Roč. 21, č. 5 (2004), s. 681-691 ISSN 1074-7613 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : NTAL * Grb2 * lymphocyte Subject RIV: EC - Immunology Impact factor: 15.448, year: 2004

  7. 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.

  8. 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.

  9. Novel adapter proteins that link the human GM-CSF receptor to the phosphatidylino-sitol 3-kinase and Shc/Grb2/ras signaling pathways.

    Science.gov (United States)

    Jücker, M; Feldman, R A

    1996-01-01

    We have used a human GM-CSF-dependent hematopoietic cell line that responds to physiological concentrations of hGM-CSF to analyze a set of signaling events that occur in normal myelopoiesis and whose deregulation may lead to leukemogenesis. Stimulation of these cells with hGM-CSF induced the assembly of multimeric complexes that contained known and novel phosphotyrosyl proteins. One of the new proteins was a major phosphotyrosyl substrate of 76-85 kDa (p80) that was directly associated with the p85 subunit of phosphatidylinositol (PI) 3-kinase through the SH2 domains of p85. p80 also associated with the beta subunit of the activated hGM-CSF receptor, and assembly of this complex correlated with activation of PI 3-kinase. A second phosphotyrosyl protein we identified, p140, associated with the Shc and Grb2 adapter proteins by direct binding to a novel phosphotyrosine-interacting domain located at the N-terminus of Shc. and to the SH3 domains of Grb2, respectively. The Shc/p140/Grb2 complex was found to be constitutively activated in acute myeloid leukemia cells, indicating that activation of this pathway may be a necessary step in the development of some leukemias. The p80/p85/PI 3-kinase and the Shc/Grb2/p140 complexes were tightly associated with Src family kinases, which were prime candidates for phosphorylation of Shc, p80, p140 and other phosphotyrosyl substrates present in these complexes. Our studies suggest that p80 and p140 may link the hGM-CSF receptor to the PI 3-kinase and Shc/Grb2/ras signaling pathways, respectively, and that abnormal activation of hGM-CSF-dependent targets may play a role in leukemogenesis.

  10. DISCOVERY AND REDSHIFT OF AN OPTICAL AFTERGLOW IN 71 deg{sup 2}: iPTF13bxl AND GRB 130702A

    Energy Technology Data Exchange (ETDEWEB)

    Singer, Leo P.; Brown, Duncan A. [LIGO Laboratory, California Institute of Technology, Pasadena, CA 91125 (United States); Bradley Cenko, S.; Gehrels, Neil; McEnery, Julie [Astrophysics Science Division, NASA Goddard Space Flight Center, Mail Code 661, Greenbelt, MD 20771 (United States); Kasliwal, Mansi M.; Mulchaey, John [Observatories of the Carnegie Institution for Science, 813 Santa Barbara St, Pasadena, CA 91101 (United States); Perley, Daniel A.; Kulkarni, S. R.; Bellm, Eric; Barlow, Tom; Cao, Yi; Horesh, Assaf [Cahill Center for Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Ofek, Eran O.; Arcavi, Iair [Benoziyo Center for Astrophysics, The Weizmann Institute of Science, Rehovot 76100 (Israel); Nugent, Peter E.; Bloom, Joshua S. [Department of Astronomy, University of California Berkeley, B-20 Hearst Field Annex 3411, Berkeley, CA 94720-3411 (United States); Corsi, Alessandra [George Washington University, Corcoran Hall, Washington, DC 20052 (United States); Frail, Dale A. [National Radio Astronomy Observatory, P.O. Box O, Socorro, NM 87801 (United States); Masci, Frank J., E-mail: lsinger@caltech.edu [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); and others

    2013-10-20

    We report the discovery of the optical afterglow of the γ-ray burst (GRB) 130702A, identified upon searching 71 deg{sup 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.

  11. 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.

  12. 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.

  13. 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

  14. The fifth adaptor protein complex.

    Directory of Open Access Journals (Sweden)

    Jennifer Hirst

    2011-10-01

    Full Text Available Adaptor protein (AP complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent mannose 6-phosphate receptor and causes the cell to form swollen endosomal structures with emanating tubules. AP-5 subunits can be found in all five eukaryotic supergroups, but they have been co-ordinately lost in many organisms. Concatenated phylogenetic analysis provides robust resolution, for the first time, into the evolutionary order of emergence of the adaptor subunit families, showing AP-3 as the basal complex, followed by AP-5, AP-4, and AP-1 and AP-2. Thus, AP-5 is an evolutionarily ancient complex, which is involved in endosomal sorting, and which has links with hereditary spastic paraplegia.

  15. 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 ...

  16. Modularly Constructed Synthetic Granzyme B Molecule Enables Interrogation of Intracellular Proteases for Targeted Cytotoxicity.

    Science.gov (United States)

    Ho, Patrick; Ede, Christopher; Chen, Yvonne Y

    2017-08-18

    Targeted therapies promise to increase the safety and efficacy of treatments against diseases ranging from cancer to viral infections. However, the vast majority of targeted therapeutics relies on the recognition of extracellular biomarkers, which are rarely restricted to diseased cells and are thus prone to severe and sometimes-fatal off-target toxicities. In contrast, intracellular antigens present a diverse yet underutilized repertoire of disease markers. Here, we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein VErifier and Response Trigger (COVERT)-which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity. COVERT molecules consist of the cytotoxic protein granzyme B (GrB) fused to an inhibitory N-terminal peptide, which can be removed by researcher-specified proteases to activate GrB function. We demonstrate that fusion of a small ubiquitin-like modifier 1 (SUMO1) protein to GrB yields a SUMO-GrB molecule that is specifically activated by the cancer-associated sentrin-specific protease 1 (SENP1). SUMO-GrB selectively triggers apoptotic phenotypes in HEK293T cells that overexpress SENP1, and it is highly sensitive to different SENP1 levels across cell lines. We further demonstrate the rational design of additional COVERT molecules responsive to enterokinase (EK) and tobacco etch virus protease (TEVp), highlighting the COVERT platform's modularity and adaptability to diverse protease targets. As an initial step toward engineering COVERT-T cells for adoptive T-cell therapy, we verified that primary human T cells can express, package, traffic, and deliver engineered GrB molecules in response to antigen stimulation. Our findings set the foundation for future intracellular-antigen-responsive therapeutics that can complement surface-targeted therapies.

  17. 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...

  18. A dimer of the Toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins.

    Directory of Open Access Journals (Sweden)

    Ricardo Núñez Miguel

    2007-08-01

    Full Text Available The Toll-like receptor 4 (TLR4 is a class I transmembrane receptor expressed on the surface of immune system cells. TLR4 is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and forms part of the innate immune response in mammals. Like other class 1 receptors, TLR4 is activated by ligand induced dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR signalling domain. This homodimerization event is proposed to provide a new scaffold that is able to bind downstream signalling adaptor proteins. TLR4 uses two different sets of adaptors; TRAM and TRIF, and Mal and MyD88. These adaptor pairs couple two distinct signalling pathways leading to the activation of interferon response factor 3 (IRF-3 and nuclear factor kappaB (NFkappaB respectively. In this paper we have generated a structural model of the TLR4 TIR dimer and used molecular docking to probe for potential sites of interaction between the receptor homodimer and the adaptor molecules. Remarkably, both the Mal and TRAM adaptors are strongly predicted to bind at two symmetry-related sites at the homodimer interface. This model of TLR4 activation is supported by extensive functional studies involving site directed mutagenesis, inhibition by cell permeable peptides and stable protein phosphorylation of receptor and adaptor TIR domains. Our results also suggest a molecular mechanism for two recent findings, the caspase 1 dependence of Mal signalling and the protective effects conferred by the Mal polymorphism Ser180Leu.

  19. 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

  20. 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...

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. Stepping motor adaptor actuator for a commercial uhv linear motion feedthrough

    International Nuclear Information System (INIS)

    Iarocci, M.; Oversluizen, T.

    1989-01-01

    An adaptor coupling has been developed that will allow the attachment of a standard stepping motor to a precision commercial (Varian) uhv linear motion feedthrough. The assembly, consisting of the motor, motor adaptor, limit switches, etc. is clamped to the feedthrough body which can be done under vacuum conditions if necessary. With a 500 step/rev. stepping motor the resolution is 1.27 μm per step. We presently use this assembly in a remote location for the precise positioning of a beam sensing monitor. 2 refs., 3 figs

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. A Big-Five Personality Profile of the Adaptor and Innovator.

    Science.gov (United States)

    Kwang, Ng Aik; Rodrigues, Daphne

    2002-01-01

    A study explored the relationship between two creative types (adaptor and innovator) and the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), in 164 teachers in Singapore. Adaptors were significantly more conscientious than innovators, while innovators were significantly more…

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. Adaptor Protein Complex 2 (AP-2) Mediated, Clathrin Dependent Endocytosis, And Related Gene Activities, Are A Prominent Feature During Maturation Stage Amelogenesis

    Science.gov (United States)

    LACRUZ, Rodrigo S.; BROOKES, Steven J.; WEN, Xin; JIMENEZ, Jaime M.; VIKMAN, Susanna; HU, Ping; WHITE, Shane N.; LYNGSTADAAS, S. Petter; OKAMOTO, Curtis T.; SMITH, Charles E.; PAINE, Michael L.

    2012-01-01

    Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real time PCR, we show that the expression of clathrin and adaptor protein subunits are up-regulated in maturation stage rodent enamel organ cells. AP-2 is the most up-regulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin dependent endocytosis, thus implying the likelihood of a specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also up-regulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1), cluster of differentiation 63 and 68 (Cd63 and Cd68), ATPase, H+ transporting, lysosomal V0 subunit D2 (Atp6v0d2), ATPase, H+ transporting, lysosomal V1 subunit B2 (Atp6v1b2), chloride channel, voltage-sensitive 7 (Clcn7) and cathepsin K (Ctsk). Immunohistological data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain® showed up-regulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor regulated pathway for the endocytosis of enamel matrix proteins. These data together

  20. NECAPs are negative regulators of the AP2 clathrin adaptor complex.

    Science.gov (United States)

    Beacham, Gwendolyn M; Partlow, Edward A; Lange, Jeffrey J; Hollopeter, Gunther

    2018-01-18

    Eukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss of ncap-1 , the sole C. elegans gene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2 in vitro and localize with constitutively open AP2 mutants in vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2. © 2018, Beacham et al.

  1. 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.

  2. The adaptor molecule signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is essential in mechanisms involving the Fyn tyrosine kinase for induction and progression of collagen-induced arthritis.

    Science.gov (United States)

    Zhong, Ming-Chao; Veillette, André

    2013-11-01

    Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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).

  8. 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.

  9. Regulation and function of the CD3¿ DxxxLL motif: a binding site for adaptor protein-1 and adaptor protein-2 in vitro

    DEFF Research Database (Denmark)

    Dietrich, J; Kastrup, J; Nielsen, B L

    1997-01-01

    /CD3gamma chimeras; and in vitro by binding CD3gamma peptides to clathrin-coated vesicle adaptor proteins (APs). We find that the CD3gamma D127xxxLL131/132 sequence represents one united motif for binding of both AP-1 and AP-2, and that this motif functions as an active sorting motif in monomeric CD4...... and for AP binding in vitro. Furthermore, we provide evidence indicating that phosphorylation of CD3gamma S126 in the context of the complete TCR induces a conformational change that exposes the DxxxLL sequence for AP binding. Exposure of the DxxxLL motif causes an increase in the TCR internalization rate...

  10. 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.

  11. 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.

  12. 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...

  13. THE UNCOVERING OF A NOVEL REGULATORY MECHANISM FOR PLD2: FORMATION OF A TERNARY COMPLEX WITH PROTEIN TYROSINE PHOSPHATASE PTP1B AND GROWTH FACTOR RECEPTOR-BOUND PROTEIN GRB2

    Science.gov (United States)

    Horn, Jeff; Lopez, Isabel; Miller, Mill; Gomez-Cambronero, Julian

    2011-01-01

    The regulation of PLD2 activation is poorly understood at present. Transient transfection of COS-7 with a mycPLD2 construct results in elevated levels of PLD2 enzymatic activity and tyrosyl phosphorylation. To investigate whether this phosphorylation affects PLD2 enzymatic activity, anti-myc immunoprecipitates were treated with recombinant protein tyrosine phosphatase PTP1B. Surprisingly, lipase activity and PY levels both increased over a range of PTP1B concentrations. These increases occurred in parallel to a measurable PTP1B-associated phosphatase activity. Inhibitor studies demonstrated that an EGF-receptor type kinase is involved in phosphorylation. In a COS-7 cell line created in the laboratory that stably expressed myc-PLD2, PTP1B induced a robust (>6-fold) augmentation of myc-PLD2 phosphotyrosine content. The addition of growth factor receptor-bound protein 2 (Grb2) to cell extracts also elevated PY levels of myc-PLD (>10-fold). Systematic co-immunoprecipitation-immunoblotting experiments pointed at a physical association between PLD2, Grb2 and PTP1B in both physiological conditions and in overexpressed cells. This is the first report of a demonstration of the mammalian isoform PLD2 existing in a ternary complex with a protein tyrosine phosphatase, PTP1b, and the docking protein Grb2 which greatly enhances tyrosyl phosphorylation of the lipase. PMID:15896299

  14. Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.

    OpenAIRE

    Raabe, T; Olivier, J P; Dickson, B J; Liu, X; Gish, G D; Pawson, T; Hafen, E

    1995-01-01

    The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. We have used a combined biochemical and genetic approach to study the interactions between Sev, Drk and Sos. We show that Tyr2546 in the cytoplasmic tail of Sev is r...

  15. 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...

  16. 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.

  17. DMPD: The SAP family of adaptors in immune regulation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15541655 The SAP family of adaptors in immune regulation. Latour S, Veillette A. Se...min Immunol. 2004 Dec;16(6):409-19. (.png) (.svg) (.html) (.csml) Show The SAP family of adaptors in immune ...regulation. PubmedID 15541655 Title The SAP family of adaptors in immune regulation. Authors Latour S, Veill

  18. 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)

  19. 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

  20. TRAM is involved in IL-18 signaling and functions as a sorting adaptor for MyD88.

    Directory of Open Access Journals (Sweden)

    Hidenori Ohnishi

    Full Text Available MyD88, a Toll/interleukin-1 receptor homology (TIR domain-containing adaptor protein, mediates signals from the Toll-like receptors (TLR or IL-1/IL-18 receptors to downstream kinases. In MyD88-dependent TLR4 signaling, the function of MyD88 is enhanced by another TIR domain-containing adaptor, Mal/TIRAP, which brings MyD88 to the plasma membrane and promotes its interaction with the cytosolic region of TLR4. Hence, Mal is recognized as the "sorting adaptor" for MyD88. In this study, a direct interaction between MyD88-TIR and another membrane-sorting adaptor, TRAM/TICAM-2, was demonstrated in vitro. Cell-based assays including RNA interference experiments and TRAM deficient mice revealed that the interplay between MyD88 and TRAM in cells is important in mediating IL-18 signal transduction. Live cell imaging further demonstrated the co-localized accumulation of MyD88 and TRAM in the membrane regions in HEK293 cells. These findings suggest that TRAM serves as the sorting adaptor for MyD88 in IL-18 signaling, which then facilitates the signal transduction. The binding sites for TRAM are located in the TIR domain of MyD88 and actually overlap with the binding sites for Mal. MyD88, the multifunctional signaling adaptor that works together with most of the TLR members and with the IL-1/IL-18 receptors, can interact with two distinct sorting adaptors, TRAM and Mal, in a conserved manner in a distinct context.

  1. 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 ...

  2. Study on the isothermal forging process of MB26 magnesium alloy adaptor

    Directory of Open Access Journals (Sweden)

    Xu Wenchen

    2015-01-01

    Full Text Available The isothermal forging process is an effective method to manufacture complex-shaped components of hard-to-work materials, such as magnesium alloys. This study investigates the isothermal forging process of an MB26 magnesium alloy adaptor with three branches. The results show that two-step forging process is appropriate to form the adaptor forging, which not only improves the filling quality but also reduces the forging load compared with one-step forging process. Moreover, the flow line is distributed along the contour of the complex-shaped adaptor forging.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Stimulation through the T cell receptor induces Cbl association with Crk proteins and the guanine nucleotide exchange protein C3G

    NARCIS (Netherlands)

    Reedquist, K. A.; Fukazawa, T.; Panchamoorthy, G.; Langdon, W. Y.; Shoelson, S. E.; Druker, B. J.; Band, H.

    1996-01-01

    We and others have recently identified Cbl, the protein product of the c-cbl protooncogene, as an early tyrosine kinase substrate upon T cell activation and have shown that Cbl forms in vivo complexes with Src family tyrosine kinases, Grb2 adaptor protein, and the p85 subunit of PI-3 kinase. Here we

  8. 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

  9. 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

  10. Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage.

    Science.gov (United States)

    Qian, Suhong; Fan, Wenchun; Liu, Tingting; Wu, Mengge; Zhang, Huawei; Cui, Xiaofang; Zhou, Yun; Hu, Junjie; Wei, Shaozhong; Chen, Huanchun; Li, Xiangmin; Qian, Ping

    2017-08-15

    Seneca Valley virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anticancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial antiviral signaling (MAVS), Toll/interleukin 1 (IL-1) receptor domain-containing adaptor inducing IFN-β (TRIF), and TRAF family member-associated NF-κB activator (TANK), via viral 3C protease (3C pro ). SVV 3C pro mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity. The cleaved MAVS, TRIF, and TANK lost the ability to regulate pattern recognition receptor (PRR)-mediated IFN production. The cleavage of TANK also facilitated TRAF6-induced NF-κB activation. SVV was also found to be sensitive to IFN-β. Therefore, SVV suppressed antiviral IFN production to escape host antiviral innate immune responses by cleaving host adaptor molecules. IMPORTANCE Host cells have developed various defenses against microbial pathogen infection. The production of IFN is the first line of defense against microbial infection. However, viruses have evolved many strategies to disrupt this host defense. SVV, a member of the Picornavirus genus, is an oncolytic virus that shows potential functions in anticancer therapy. It has been demonstrated that IFN can be used in anticancer therapy for certain tumors. However, the relationship between oncolytic virus and innate immune response in anticancer therapy is still not well known. In this study, we showed that SVV has evolved as an effective mechanism to inhibit host type I IFN production by using its 3C pro to cleave the molecules MAVS, TRIF, and TANK directly. These molecules are crucial for

  11. Surface plasmon resonance thermodynamic and kinetic analysis as a strategic tool in drug design. Distinct ways for phosphopeptides to plug into Src- and Grb2 SH2 domains

    NARCIS (Netherlands)

    de Mol, Nico J; Dekker, Frank J; Broutin, Isabel; Fischer, Marcel J E; Liskamp, Rob M J; Dekker, Frank

    2005-01-01

    Thermodynamic and kinetic studies of biomolecular interactions give insight into specificity of molecular recognition processes and advance rational drug design. Binding of phosphotyrosine (pY)-containing peptides to Src- and Grb2-SH2 domains was investigated using a surface plasmon resonance

  12. Adaptor protein complex 2-mediated, clathrin-dependent endocytosis, and related gene activities, are a prominent feature during maturation stage amelogenesis.

    Science.gov (United States)

    Lacruz, Rodrigo S; Brookes, Steven J; Wen, Xin; Jimenez, Jaime M; Vikman, Susanna; Hu, Ping; White, Shane N; Lyngstadaas, S Petter; Okamoto, Curtis T; Smith, Charles E; Paine, Michael L

    2013-03-01

    Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real-time PCR, we show that the expression of clathrin and adaptor protein subunits are upregulated in maturation stage rodent enamel organ cells. AP complex 2 (AP-2) is the most upregulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts, with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin-dependent endocytosis, thus implying the likelihood of specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also upregulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1); cluster of differentiation 63 and 68 (Cd63 and Cd68); ATPase, H(+) transporting, lysosomal V0 subunit D2 (Atp6v0d2); ATPase, H(+) transporting, lysosomal V1 subunit B2 (Atp6v1b2); chloride channel, voltage-sensitive 7 (Clcn7); and cathepsin K (Ctsk). Immunohistologic data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain showed upregulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor-regulated pathway for the endocytosis of enamel matrix proteins. These data

  13. 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

  14. 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.

  15. Ntal/Lab/Lat2

    DEFF Research Database (Denmark)

    Iwaki, Shoko; Jensen, Bettina M; Gilfillan, Alasdair M

    2007-01-01

    T cells. As demonstrated in monocytes and B cells, phosphorylated NTAL/LAB/LAT2 recruits signaling molecules such as Grb2, Gab1 and c-Cbl into receptor-signaling complexes. Although gene knock out and knock down studies have indicated that NTAL/LAB/LAT2 may function as both a positive and negative...

  16. 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.

  17. 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

  18. PAG - a multipurpose transmembrane adaptor protein

    Czech Academy of Sciences Publication Activity Database

    Hrdinka, Matouš; Hořejší, Václav

    2014-01-01

    Roč. 33, č. 41 (2014), s. 4881-4892 ISSN 0950-9232 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : PAG * adaptor protein * membrane raft Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.459, year: 2014

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. The AP2 clathrin adaptor protein complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.

    Science.gov (United States)

    Garafalo, Steven D; Luth, Eric S; Moss, Benjamin J; Monteiro, Michael I; Malkin, Emily; Juo, Peter

    2015-05-15

    Regulation of glutamate receptor (GluR) abundance at synapses by clathrin-mediated endocytosis can control synaptic strength and plasticity. We take advantage of viable, null mutations in subunits of the clathrin adaptor protein 2 (AP2) complex in Caenorhabditis elegans to characterize the in vivo role of AP2 in GluR trafficking. In contrast to our predictions for an endocytic adaptor, we found that levels of the GluR GLR-1 are decreased at synapses in the ventral nerve cord (VNC) of animals with mutations in the AP2 subunits APM-22, APA-2/α, or APS-22. Rescue experiments indicate that APM-22 functions in glr-1-expressing interneurons and the mature nervous system to promote GLR-1 levels in the VNC. Genetic analyses suggest that APM-22 acts upstream of GLR-1 endocytosis in the VNC. Consistent with this, GLR-1 accumulates in cell bodies of apm-2 mutants. However, GLR-1 does not appear to accumulate at the plasma membrane of the cell body as expected, but instead accumulates in intracellular compartments including Syntaxin-13- and RAB-14-labeled endosomes. This study reveals a novel role for the AP2 clathrin adaptor in promoting the abundance of GluRs at synapses in vivo, and implicates AP2 in the regulation of GluR trafficking at an early step in the secretory pathway. © 2015 Garafalo et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. Models of crk adaptor proteins in cancer.

    Science.gov (United States)

    Bell, Emily S; Park, Morag

    2012-05-01

    The Crk family of adaptor proteins (CrkI, CrkII, and CrkL), originally discovered as the oncogene fusion product, v-Crk, of the CT10 chicken retrovirus, lacks catalytic activity but engages with multiple signaling pathways through their SH2 and SH3 domains. Crk proteins link upstream tyrosine kinase and integrin-dependent signals to downstream effectors, acting as adaptors in diverse signaling pathways and cellular processes. Crk proteins are now recognized to play a role in the malignancy of many human cancers, stimulating renewed interest in their mechanism of action in cancer progression. The contribution of Crk signaling to malignancy has been predominantly studied in fibroblasts and in hematopoietic models and more recently in epithelial models. A mechanistic understanding of Crk proteins in cancer progression in vivo is still poorly understood in part due to the highly pleiotropic nature of Crk signaling. Recent advances in the structural organization of Crk domains, new roles in kinase regulation, and increased knowledge of the mechanisms and frequency of Crk overexpression in human cancers have provided an incentive for further study in in vivo models. An understanding of the mechanisms through which Crk proteins act as oncogenic drivers could have important implications in therapeutic targeting.

  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. Detection of a rare BCR-ABL tyrosine kinase fusion protein in H929 multiple myeloma cells using immunoprecipitation (IP)-tandem mass spectrometry (MS/MS).

    Science.gov (United States)

    Breitkopf, Susanne B; Yuan, Min; Pihan, German A; Asara, John M

    2012-10-02

    Hypothesis directed proteomics offers higher throughput over global analyses. We show that immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) in H929 multiple myeloma (MM) cancer cells led to the discovery of a rare and unexpected BCR-ABL fusion, informing a therapeutic intervention using imatinib (Gleevec). BCR-ABL is the driving mutation in chronic myeloid leukemia (CML) and is uncommon to other cancers. Three different IP-MS experiments central to cell signaling pathways were sufficient to discover a BCR-ABL fusion in H929 cells: phosphotyrosine (pY) peptide IP, p85 regulatory subunit of phosphoinositide-3-kinase (PI3K) IP, and the GRB2 adaptor IP. The pY peptides inform tyrosine kinase activity, p85 IP informs the activating adaptors and receptor tyrosine kinases (RTKs) involved in AKT activation and GRB2 IP identifies RTKs and adaptors leading to ERK activation. Integration of the bait-prey data from the three separate experiments identified the BCR-ABL protein complex, which was confirmed by biochemistry, cytogenetic methods, and DNA sequencing revealed the e14a2 fusion transcript. The tyrosine phosphatase SHP2 and the GAB2 adaptor protein, important for MAPK signaling, were common to all three IP-MS experiments. The comparative treatment of tyrosine kinase inhibitor (TKI) drugs revealed only imatinib, the standard of care in CML, was inhibitory to BCR-ABL leading to down-regulation of pERK and pS6K and inhibiting cell proliferation. These data suggest a model for directed proteomics from patient tumor samples for selecting the appropriate TKI drug(s) based on IP and LC-MS/MS. The data also suggest that MM patients, in addition to CML patients, may benefit from BCR-ABL diagnostic screening.

  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. Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission

    OpenAIRE

    Kittler, Josef T.; Chen, Guojun; Honing, Stephan; Bogdanov, Yury; McAinsh, Kristina; Arancibia-Carcamo, I. Lorena; Jovanovic, Jasmina N.; Pangalos, Menelas N.; Haucke, Volker; Yan, Zhen; Moss, Stephen J.

    2005-01-01

    The efficacy of synaptic inhibition depends on the number of γ-aminobutyric acid type A receptors (GABAARs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABAAR endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABAAR β subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the β3 subunit) incorporates...

  9. 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.

  10. The Emerging and Diverse Roles of Src-Like Adaptor Proteins in Health and Disease

    Directory of Open Access Journals (Sweden)

    Nikolett Marton

    2015-01-01

    Full Text Available Although Src-like adaptor proteins (SLAP-1 and SLAP-2 were mainly studied in lymphocytes, where they act as negative regulators and provide fine control of receptor signaling, recently, several other functions of these proteins were discovered. In addition to the well-characterized immunoregulatory functions, SLAP proteins appear to have an essential role in the pathogenesis of type I hypersensitivity, osteoporosis, and numerous malignant diseases. Both adaptor proteins are expressed in a wide variety of tissues, where they have mostly inhibitory effects on multiple intracellular signaling pathways. In this review, we summarize the diverse effects of SLAP proteins.

  11. 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

  12. 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.

  13. The 2175 Å Extinction Feature in the Optical Afterglow Spectrum of GRB 180325A at z = 2.25

    Science.gov (United States)

    Zafar, T.; Heintz, K. E.; Fynbo, J. P. U.; Malesani, D.; Bolmer, J.; Ledoux, C.; Arabsalmani, M.; Kaper, L.; Campana, S.; Starling, R. L. C.; Selsing, J.; Kann, D. A.; de Ugarte Postigo, A.; Schweyer, T.; Christensen, L.; Møller, P.; Japelj, J.; Perley, D.; Tanvir, N. R.; D’Avanzo, P.; Hartmann, D. H.; Hjorth, J.; Covino, S.; Sbarufatti, B.; Jakobsson, P.; Izzo, L.; Salvaterra, R.; D’Elia, V.; Xu, D.

    2018-06-01

    The ultraviolet (UV) extinction feature at 2175 Å is ubiquitously observed in the Galaxy but is rarely detected at high redshifts. Here we report the spectroscopic detection of the 2175 Å bump on the sightline to the γ-ray burst (GRB) afterglow GRB 180325A at z = 2.2486, the only unambiguous detection over the past 10 years of GRB follow-up, at four different epochs with the Nordic Optical Telescope (NOT) and the Very Large Telescope (VLT)/X-shooter. Additional photometric observations of the afterglow are obtained with the Gamma-Ray burst Optical and Near-Infrared Detector (GROND). We construct the near-infrared to X-ray spectral energy distributions (SEDs) at four spectroscopic epochs. The SEDs are well described by a single power law and an extinction law with R V ≈ 4.4, A V ≈ 1.5, and the 2175 Å extinction feature. The bump strength and extinction curve are shallower than the average Galactic extinction curve. We determine a metallicity of [Zn/H] > ‑0.98 from the VLT/X-shooter spectrum. We detect strong neutral carbon associated with the GRB with equivalent width of W r(λ 1656) = 0.85 ± 0.05. We also detect optical emission lines from the host galaxy. Based on the Hα emission-line flux, the derived dust-corrected star formation rate is ∼46 ± 4 M ⊙ yr‑1 and the predicted stellar mass is log M */M ⊙ ∼ 9.3 ± 0.4, suggesting that the host galaxy is among the main-sequence star-forming galaxies. Based on observations made with the Nordic Optical Telescope, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO program 0100.D‑0649(A).

  14. A transgenic Drosophila model demonstrates that the Helicobacter pylori CagA protein functions as a eukaryotic Gab adaptor.

    Directory of Open Access Journals (Sweden)

    Crystal M Botham

    2008-05-01

    Full Text Available Infection with the human gastric pathogen Helicobacter pylori is associated with a spectrum of diseases including gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. The cytotoxin-associated gene A (CagA protein of H. pylori, which is translocated into host cells via a type IV secretion system, is a major risk factor for disease development. Experiments in gastric tissue culture cells have shown that once translocated, CagA activates the phosphatase SHP-2, which is a component of receptor tyrosine kinase (RTK pathways whose over-activation is associated with cancer formation. Based on CagA's ability to activate SHP-2, it has been proposed that CagA functions as a prokaryotic mimic of the eukaryotic Grb2-associated binder (Gab adaptor protein, which normally activates SHP-2. We have developed a transgenic Drosophila model to test this hypothesis by investigating whether CagA can function in a well-characterized Gab-dependent process: the specification of photoreceptors cells in the Drosophila eye. We demonstrate that CagA expression is sufficient to rescue photoreceptor development in the absence of the Drosophila Gab homologue, Daughter of Sevenless (DOS. Furthermore, CagA's ability to promote photoreceptor development requires the SHP-2 phosphatase Corkscrew (CSW. These results provide the first demonstration that CagA functions as a Gab protein within the tissue of an organism and provide insight into CagA's oncogenic potential. Since many translocated bacterial proteins target highly conserved eukaryotic cellular processes, such as the RTK signaling pathway, the transgenic Drosophila model should be of general use for testing the in vivo function of bacterial effector proteins and for identifying the host genes through which they function.

  15. CD6 and Linker of Activated T Cells are Potential Interaction Partners for T Cell-Specific Adaptor Protein.

    Science.gov (United States)

    Hem, C D; Ekornhol, M; Granum, S; Sundvold-Gjerstad, V; Spurkland, A

    2017-02-01

    The T cell-specific adaptor protein (TSAd) contains several protein interaction domains, and is merging as a modulator of T cell activation. Several interaction partners for the TSAd proline-rich region and phosphotyrosines have been identified, including the Src and Tec family kinases lymphocyte-specific protein tyrosine kinase and interleukin 2-inducible T cell kinase. Via its Src homology 2 (SH2) domain, TSAd may thus function as a link between these enzymes and other signalling molecules. However, few binding partners to the TSAd SH2 domain in T cells are hitherto known. Through the use of in silico ligand prediction, peptide spot arrays, pull-down and immunoprecipitation experiments, we here report novel interactions between the TSAd SH2 domain and CD6 phosphotyrosine (pTyr) 629 and linker of activated T cells (LAT) pTyr 171 , pTyr 191 and pTyr 226 . © 2016 The Foundation for the Scandinavian Journal of Immunology.

  16. 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

  17. Aftereffects of Spectrally Similar and Dissimilar Spectral Motion Adaptors in the Tritone Paradox

    Directory of Open Access Journals (Sweden)

    Stephanie Malek

    2018-05-01

    Full Text Available Shepard tones consist of octave-spaced components, whose amplitudes are generated under a fixed bell-shaped spectral envelope. They are well defined in pitch chroma, but generate octave confusions that in turn can produce ambiguities in the perceived relative pitch heights when their chromas are exactly a tritone apart (the tritone paradox. This study examined the effects of tonal context on relative pitch height judgments using adaptor sequences followed by target sequences (pairs of Shepard tones of different chromas separated by a tritone. Listeners judged whether the second target Shepard tone was higher or lower than the first. Adaptor sequences consisted of rising or falling scales (43 s at the beginning of each block, 4 s before each target sequence. Two sets of Shepard tones were used for adaptors and targets that were generated under spectral envelopes centered at either A3 (220 Hz and C6 (1,046 Hz. Pitch direction judgments (rising vs. falling to spectrally consistent (A3–A3, C6–C6 and inconsistent (A3–C6, C6–A3 adaptor-target combinations were studied. Large significant contrastive aftereffects (0.08–0.21 change in fraction of pitch direction responses were only found for the Shepard tones that were judged as higher in the control condition (judgments about the target sequences without adaptor sequences for the consistent adaptor-target conditions (A3–A3, C6–C6. The experiments rule out explanations based on non-sensory decision making processes. Possible explanations in terms of perceptual aftereffects caused by adaptation in central auditory frequency-motion detectors are discussed.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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....

  4. Palmitoylated transmembrane adaptor proteins in leukocyte signaling

    Czech Academy of Sciences Publication Activity Database

    Štěpánek, Ondřej; Dráber, Peter; Hořejší, Václav

    2014-01-01

    Roč. 26, č. 5 (2014), s. 895-902 ISSN 0898-6568 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : Leukocyte * Adaptor * Palmitoylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.315, year: 2014

  5. 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.

  6. Bottom nozzle for nuclear reactor fuel assembly having an adaptor plate and a coupled filtration plate

    International Nuclear Information System (INIS)

    Verdier, M.; Mortgat, R.

    1992-01-01

    The bottom nozzle includes an adaptor plate with openings to allow the passage of water and a filtration plate with small holes. The openings in the adaptor plate are symmetrical with regard to medians and diagonals. Within each zone, some of the openings are rectangular and some may be circular. The small holes in the filtration plate coincide with the rectangular openings in the adaptor plate

  7. 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.

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Insight into Phosphatidylinositol-Dependent Membrane Localization of the Innate Immune Adaptor Protein Toll/Interleukin 1 Receptor Domain-Containing Adaptor Protein

    Directory of Open Access Journals (Sweden)

    Mahesh Chandra Patra

    2018-01-01

    Full Text Available The toll/interleukin 1 receptor (TIR domain-containing adaptor protein (TIRAP plays an important role in the toll-like receptor (TLR 2, TLR4, TLR7, and TLR9 signaling pathways. TIRAP anchors to phosphatidylinositol (PI 4,5-bisphosphate (PIP2 on the plasma membrane and PI (3,4,5-trisphosphate (PIP3 on the endosomal membrane and assists in recruitment of the myeloid differentiation primary response 88 protein to activated TLRs. To date, the structure and mechanism of TIRAP’s membrane association are only partially understood. Here, we modeled an all-residue TIRAP dimer using homology modeling, threading, and protein–protein docking strategies. Molecular dynamics simulations revealed that PIP2 creates a stable microdomain in a dipalmitoylphosphatidylcholine bilayer, providing TIRAP with its physiologically relevant orientation. Computed binding free energy values suggest that the affinity of PI-binding domain (PBD for PIP2 is stronger than that of TIRAP as a whole for PIP2 and that the short PI-binding motif (PBM contributes to the affinity between PBD and PIP2. Four PIP2 molecules can be accommodated by distinct lysine-rich surfaces on the dimeric PBM. Along with the known PI-binding residues (K15, K16, K31, and K32, additional positively charged residues (K34, K35, and R36 showed strong affinity toward PIP2. Lysine-to-alanine mutations at the PI-binding residues abolished TIRAP’s affinity for PIP2; however, K34, K35, and R36 consistently interacted with PIP2 headgroups through hydrogen bond (H-bond and electrostatic interactions. TIRAP exhibited a PIP2-analogous intermolecular contact and binding affinity toward PIP3, aided by an H-bond network involving K34, K35, and R36. The present study extends our understanding of TIRAP’s membrane association, which could be helpful in designing peptide decoys to block TLR2-, TLR4-, TLR7-, and TLR9-mediated autoimmune diseases.

  14. 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.

  15. 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.

  16. 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

  17. 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,

  18. An Adaptor Domain-Mediated Auto-Catalytic Interfacial Kinase Reaction

    Science.gov (United States)

    Liao, Xiaoli; Su, Jing; Mrksich, Milan

    2010-01-01

    This paper describes a model system for studying the auto-catalytic phosphorylation of an immobilized substrate by a kinase enzyme. This work uses self-assembled monolayers (SAMs) of alkanethiolates on gold to present the peptide substrate on a planar surface. Treatment of the monolayer with Abl kinase results in phosphorylation of the substrate. The phosphorylated peptide then serves as a ligand for the SH2 adaptor domain of the kinase and thereby directs the kinase activity to nearby peptide substrates. This directed reaction is intramolecular and proceeds with a faster rate than does the initial, intermolecular reaction, making this an auto-catalytic process. The kinetic non-linearity gives rise to properties that have no counterpart in the corresponding homogeneous phase reaction: in one example, the rate for phosphorylation of a mixture of two peptides is faster than the sum of the rates for phosphorylation of each peptide when presented alone. This work highlights the use of an adaptor domain in modulating the activity of a kinase enzyme for an immobilized substrate and offers a new approach for studying biochemical reactions in spatially inhomogeneous settings. PMID:19821459

  19. 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...

  20. Enhancement of B-cell receptor signaling by a point mutation of adaptor protein 3BP2 identified in human inherited disease cherubism.

    Science.gov (United States)

    Ogi, Kazuhiro; Nakashima, Kenji; Chihara, Kazuyasu; Takeuchi, Kenji; Horiguchi, Tomoko; Fujieda, Shigeharu; Sada, Kiyonao

    2011-09-01

    Tyrosine phosphorylation of adaptor protein c-Abl-Src homology 3 (SH3) domain-binding protein-2 (3BP2, also referred to SH3BP2) positively regulates the B-cell antigen receptor (BCR)-mediated signal transduction, leading to the activation of nuclear factor of activated T cells (NFAT). Here we showed the effect of the proline to arginine substitution of 3BP2 in which is the most common mutation in patients with cherubism (P418R) on B-cell receptor signaling. Comparing to the wild type, overexpression of the mutant form of 3BP2 (3BP2-P416R, corresponding to P418R in human protein) enhanced BCR-mediated activation of NFAT. 3BP2-P416R increased the signaling complex formation with Syk, phospholipase C-γ2 (PLC-γ2), and Vav1. In contrast, 3BP2-P416R could not change the association with the negative regulator 14-3-3. Loss of the association mutant that was incapable to associate with 14-3-3 could not mimic BCR-mediated NFAT activation in Syk-deficient cells. Moreover, BCR-mediated phosphorylation of extracellular signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) was not affected by P416R mutation. These results showed that P416R mutation of 3BP2 causes the gain of function in B cells by increasing the interaction with specific signaling molecules. © 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

  1. 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....

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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,

  8. 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.

  9. 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

  10. Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl.

    Science.gov (United States)

    Odai, H; Sasaki, K; Iwamatsu, A; Nakamoto, T; Ueno, H; Yamagata, T; Mitani, K; Yazaki, Y; Hirai, H

    1997-04-15

    Grb2/Ash and Shc are the adapter proteins that link tyrosine-kinase receptors to Ras and make tyrosine-kinase functionally associated with receptors and Ras in fibroblasts and hematopoietic cells. Grb2/Ash and Shc have the SH3, SH2, or phosphotyrosine binding domains. These domains bind to proteins containing proline-rich regions or tyrosine-phosphorylated proteins and contribute to the association of Grb2/Ash and Shc with other signaling molecules. However, there could remain unidentified signaling molecules that physically and functionally interact with these adapter proteins and have biologically important roles in the signaling pathways. By using the GST fusion protein including the full length of Grb2/Ash, we have found that c-Cbl and an unidentified 135-kD protein (pp135) are associated with Grb2/Ash. We have also found that they become tyrosine-phosphorylated by treatment of a human leukemia cell line, UT-7, with granulocyte-macrophage colony-stimulating factor (GM-CSF). We have purified the pp135 by using GST-Grb2/Ash affinity column and have isolated the full-length complementary DNA (cDNA) encoding the pp135 using a cDNA probe, which was obtained by the degenerate polymerase chain reaction based on a peptide sequence of the purified pp135. The cloned cDNA has 3,958 nucleotides that contain a single long open reading frame of 3,567 nucleotides, encoding a 1,189 amino acid protein with a predicted molecular weight of approximately 133 kD. The deduced amino acid sequence reveals that pp135 is a protein that has one SH2, one SH3, and one proline-rich domain. The pp135, which contains two motifs conserved among the inositol polyphosphate-5-phosphatase proteins, was shown to have the inositol polyphosphate-5-phosphatase activity. The pp135 was revealed to associate constitutively with Grb2/Ash and inducibly with Shc using UT-7 cells stimulated with GM-CSF. In the cell lines derived from human chronic myelogenous leukemia, pp135 was constitutively tyrosine

  11. 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

  12. 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.

  13. 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.

  14. The motogenic and mitogenic responses to HGF are amplified by the Shc adaptor protein

    DEFF Research Database (Denmark)

    Pelicci, G; Giordano, S; Zhen, Z

    1995-01-01

    The receptor of Hepatocyte Growth Factor-Scatter Factor (HGF) is a tyrosine kinase which regulates cell motility and growth. After ligand-induced tyrosine phosphorylation, the HGF receptor associates with the Shc adaptor, via the SH2 domain. Site-directed mutagenesis of the HGF receptor indicates...

  15. 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.

  16. Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation.

    Science.gov (United States)

    Stylli, Stanley S; Stacey, T T I; Verhagen, Anne M; Xu, San San; Pass, Ian; Courtneidge, Sara A; Lock, Peter

    2009-08-01

    Invadopodia are actin-based projections enriched with proteases, which invasive cancer cells use to degrade the extracellular matrix (ECM). The Phox homology (PX)-Src homology (SH)3 domain adaptor protein Tks5 (also known as SH3PXD2A) cooperates with Src tyrosine kinase to promote invadopodia formation but the underlying pathway is not clear. Here we show that Src phosphorylates Tks5 at Y557, inducing it to associate directly with the SH3-SH2 domain adaptor proteins Nck1 and Nck2 in invadopodia. Tks5 mutants unable to bind Nck show reduced matrix degradation-promoting activity and recruit actin to invadopodia inefficiently. Conversely, Src- and Tks5-driven matrix proteolysis and actin assembly in invadopodia are enhanced by Nck1 or Nck2 overexpression and inhibited by Nck1 depletion. We show that clustering at the plasma membrane of the Tks5 inter-SH3 region containing Y557 triggers phosphorylation at this site, facilitating Nck recruitment and F-actin assembly. These results identify a Src-Tks5-Nck pathway in ECM-degrading invadopodia that shows parallels with pathways linking several mammalian and pathogen-derived proteins to local actin regulation.

  17. Protein kinase A-induced internalization of Slack channels from the neuronal membrane occurs by adaptor protein-2/clathrin-mediated endocytosis.

    Science.gov (United States)

    Gururaj, Sushmitha; Evely, Katherine M; Pryce, Kerri D; Li, Jun; Qu, Jun; Bhattacharjee, Arin

    2017-11-24

    The sodium-activated potassium (K Na ) channel Kcnt1 (Slack) is abundantly expressed in nociceptor (pain-sensing) neurons of the dorsal root ganglion (DRG), where they transmit the large outward conductance I KNa and arbitrate membrane excitability. Slack channel expression at the DRG membrane is necessary for their characteristic firing accommodation during maintained stimulation, and reduced membrane channel density causes hyperexcitability. We have previously shown that in a pro-inflammatory state, a decrease in membrane channel expression leading to reduced Slack-mediated I KNa expression underlies DRG neuronal sensitization. An important component of the inflammatory milieu, PKA internalizes Slack channels from the DRG membrane, reduces I KNa , and produces DRG neuronal hyperexcitability when activated in cultured primary DRG neurons. Here, we show that this PKA-induced retrograde trafficking of Slack channels also occurs in intact spinal cord slices and that it is carried out by adaptor protein-2 (AP-2) via clathrin-mediated endocytosis. We provide mass spectrometric and biochemical evidence of an association of native neuronal AP-2 adaptor proteins with Slack channels, facilitated by a dileucine motif housed in the cytoplasmic Slack C terminus that binds AP-2. By creating a competitive peptide blocker of AP-2-Slack binding, we demonstrated that this interaction is essential for clathrin recruitment to the DRG membrane, Slack channel endocytosis, and DRG neuronal hyperexcitability after PKA activation. Together, these findings uncover AP-2 and clathrin as players in Slack channel regulation. Given the significant role of Slack in nociceptive neuronal excitability, the AP-2 clathrin-mediated endocytosis trafficking mechanism may enable targeting of peripheral and possibly, central neuronal sensitization. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. 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.

  19. 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.

  20. 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.

  1. Transmembrane adaptor proteins in the high-affinity IgE receptor signaling

    Czech Academy of Sciences Publication Activity Database

    Dráber, Petr; Hálová, Ivana; Levi-Schaffer, F.; Dráberová, Lubica

    2012-01-01

    Roč. 2, 11.1. (2012), s. 95 ISSN 1664-3224 R&D Projects: GA MŠk 1M0506; GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA AV ČR KAN200520701 Grant - others:AV ČR(CZ) M200520901 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : IgE receptor * LAT/LAT1 * LAX * NTAL/Lab/LAT2 * PAG/Cbp * mast cells * plasma membrane * transmembrane adaptor proteins Subject RIV: EB - Genetics ; Molecular Biology

  2. 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...

  3. The endothelial adaptor molecule TSAd is required for VEGF-induced angiogenic sprouting through junctional c-Src activation

    NARCIS (Netherlands)

    Gordon, Emma J; Fukuhara, Daisuke; Weström, Simone; Padhan, Narendra; Sjöström, Elisabet O; van Meeteren, Laurens|info:eu-repo/dai/nl/299142353; He, Liqun; Orsenigo, Fabrizio; Dejana, Elisabetta; Bentley, Katie; Spurkland, Anne; Claesson-Welsh, Lena

    2016-01-01

    Activation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by VEGF binding is critical for vascular morphogenesis. In addition, VEGF disrupts the endothelial barrier by triggering the phosphorylation and turnover of the junctional molecule VE-cadherin, a process mediated by the

  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. Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells.

    Science.gov (United States)

    Li, LiQi; Jothi, Raja; Cui, Kairong; Lee, Jan Y; Cohen, Tsadok; Gorivodsky, Marat; Tzchori, Itai; Zhao, Yangu; Hayes, Sandra M; Bresnick, Emery H; Zhao, Keji; Westphal, Heiner; Love, Paul E

    2011-02-01

    The nuclear adaptor Ldb1 functions as a core component of multiprotein transcription complexes that regulate differentiation in diverse cell types. In the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we demonstrate a critical and continuous requirement for Ldb1 in the maintenance of both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in hematopoietic progenitors resulted in the downregulation of many transcripts required for HSC maintenance. Genome-wide profiling by chromatin immunoprecipitation followed by sequencing (ChIP-Seq) identified Ldb1 complex-binding sites at highly conserved regions in the promoters of genes involved in HSC maintenance. Our results identify a central role for Ldb1 in regulating the transcriptional program responsible for the maintenance of HSCs.

  6. 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

  7. Sequence analysis of the Ras-MAPK pathway genes SOS1, EGFR & GRB2 in silver foxes (Vulpes vulpes): candidate genes for hereditary hyperplastic gingivitis.

    Science.gov (United States)

    Clark, Jo-Anna B J; Tully, Sara J; Dawn Marshall, H

    2014-12-01

    Hereditary hyperplastic gingivitis (HHG) is an autosomal recessive disease that presents with progressive gingival proliferation in farmed silver foxes. Hereditary gingival fibromatosis (HGF) is an analogous condition in humans that is genetically heterogeneous with several known autosomal dominant loci. For one locus the causative mutation is in the Son of sevenless homologue 1 (SOS1) gene. For the remaining loci, the molecular mechanisms are unknown but Ras pathway involvement is suspected. Here we compare sequences for the SOS1 gene, and two adjacent genes in the Ras pathway, growth receptor bound protein 2 (GRB2) and epidermal growth factor receptor (EGFR), between HHG-affected and unaffected foxes. We conclude that the known HGF causative mutation does not cause HHG in foxes, nor do the coding regions or intron-exon boundaries of these three genes contain any candidate mutations for fox gum disease. Patterns of molecular evolution among foxes and other mammals reflect high conservation and strong functional constraints for SOS1 and GRB2 but reveal a lineage-specific pattern of variability in EGFR consistent with mutational rate differences, relaxed functional constraints, and possibly positive selection.

  8. Advances in organometallic and protein chemistry

    OpenAIRE

    Ryan, C. P.

    2010-01-01

    This thesis describes two areas of scientific investigation. The first contains a description of a study on the synthesis of biotinylated and fluoresceinylated bromomaleimide based reagents. Upon synthesis, the ability of these reagents to add reversibly to cysteine containing proteins is investigated by a series of LCMS experiments. A single point mutant (L111C) of the SH2 domain of the Grb2 adaptor protein, containing a single cysteine residue, is chosen as an ideal protein for study. Thus ...

  9. Localization of the AP-3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins

    NARCIS (Netherlands)

    Peden, A.A.; Oorschot, V.; Hesser, B.A.; Austin, C.D.; Scheller, R.H.; Klumperman, J.

    2004-01-01

    The adaptor protein (AP) 3 adaptor complex has been implicated in the transport of lysosomal membrane proteins, but its precise site of action has remained controversial. Here, we show by immuno-electron microscopy that AP-3 is associated with budding profiles evolving from a tubular endosomal

  10. Matrilin-2, an extracellular adaptor protein, is needed for the regeneration of muscle, nerve and other tissues

    Directory of Open Access Journals (Sweden)

    Éva Korpos

    2015-01-01

    Full Text Available The extracellular matrix (ECM performs essential functions in the differentiation, maintenance and remodeling of tissues during development and regeneration, and it undergoes dynamic changes during remodeling concomitant to alterations in the cell-ECM interactions. Here we discuss recent data addressing the critical role of the widely expressed ECM protein, matrilin-2 (Matn2 in the timely onset of differentiation and regeneration processes in myogenic, neural and other tissues and in tumorigenesis. As a multiadhesion adaptor protein, it interacts with other ECM proteins and integrins. Matn2 promotes neurite outgrowth, Schwann cell migration, neuromuscular junction formation, skeletal muscle and liver regeneration and skin wound healing. Matn2 deposition by myoblasts is crucial for the timely induction of the global switch toward terminal myogenic differentiation during muscle regeneration by affecting transforming growth factor beta/bone morphogenetic protein 7/Smad and other signal transduction pathways. Depending on the type of tissue and the pathomechanism, Matn2 can also promote or suppress tumor growth.

  11. 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...

  12. 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....

  13. 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

  14. The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation.

    Science.gov (United States)

    Claudio, Estefania; Sønder, Søren Ulrik; Saret, Sun; Carvalho, Gabrielle; Ramalingam, Thirumalai R; Wynn, Thomas A; Chariot, Alain; Garcia-Perganeda, Antonio; Leonardi, Antonio; Paun, Andrea; Chen, Amy; Ren, Nina Y; Wang, Hongshan; Siebenlist, Ulrich

    2009-02-01

    IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well as in autoimmune diseases, such as rheumatoid arthritis and experimental autoimmune encephalomyelitis in animal models. IL-25 is a member of the IL-17 family of cytokines, but has been associated with Th2 responses instead and may negatively cross-regulate Th17/IL-17 responses. IL-25 can initiate an allergic asthma-like inflammation in the airways, which includes recruitment of eosinophils, mucus hypersecretion, Th2 cytokine production, and airways hyperreactivity. We demonstrate that these effects of IL-25 are entirely dependent on the adaptor protein CIKS (also known as Act1). Surprisingly, this adaptor is necessary to transmit IL-17 signals as well, despite the very distinct biologic responses that these two cytokines elicit. We identify CD11c(+) macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo.

  15. 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.

  16. 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.

  17. 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.

  18. p56Lck and p59Fyn Regulate CD28 Binding to Phosphatidylinositol 3-Kinase, Growth Factor Receptor-Bound Protein GRB-2, and T Cell-Specific Protein-Tyrosine Kinase ITK: Implications for T-Cell Costimulation

    Science.gov (United States)

    Raab, Monika; Cai, Yun-Cai; Bunnell, Stephen C.; Heyeck, Stephanie D.; Berg, Leslie J.; Rudd, Christopher E.

    1995-09-01

    T-cell activation requires cooperative signals generated by the T-cell antigen receptor ξ-chain complex (TCRξ-CD3) and the costimulatory antigen CD28. CD28 interacts with three intracellular proteins-phosphatidylinositol 3-kinase (PI 3-kinase), T cell-specific protein-tyrosine kinase ITK (formerly TSK or EMT), and the complex between growth factor receptor-bound protein 2 and son of sevenless guanine nucleotide exchange protein (GRB-2-SOS). PI 3-kinase and GRB-2 bind to the CD28 phosphotyrosine-based Tyr-Met-Asn-Met motif by means of intrinsic Src-homology 2 (SH2) domains. The requirement for tyrosine phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2 by CD28. Candidate kinases include p56Lck, p59Fyn, ξ-chain-associated 70-kDa protein (ZAP-70), and ITK. In this study, we demonstrate in coexpression studies that p56Lck and p59Fyn phosphorylate CD28 primarily at Tyr-191 of the Tyr-Met-Asn-Met motif, inducing a 3- to 8-fold increase in p85 (subunit of PI 3-kinase) and GRB-2 SH2 binding to CD28. Phosphatase digestion of CD28 eliminated binding. In contrast to Src kinases, ZAP-70 and ITK failed to induce these events. Further, ITK binding to CD28 was dependent on the presence of p56Lck and is thus likely to act downstream of p56Lck/p59Fyn in a signaling cascade. p56Lck is therefore likely to be a central switch in T-cell activation, with the dual function of regulating CD28-mediated costimulation as well as TCR-CD3-CD4 signaling.

  19. 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

  20. 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.

  1. 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...

  2. Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88.

    Science.gov (United States)

    Dunne, Aisling; Ejdeback, Mikael; Ludidi, Phumzile L; O'Neill, Luke A J; Gay, Nicholas J

    2003-10-17

    The Toll/interleukin 1 receptor (TIR) domain is a region found in the cytoplasmic tails of members of the Toll-like receptor/interleukin-1 receptor superfamily. The domain is essential for signaling and is also found in the adaptor proteins Mal (MyD88 adaptor-like) and MyD88, which function to couple activation of the receptor to downstream signaling components. Experimental structures of two Toll/interleukin 1 receptor domains reveal a alpha-beta-fold similar to that of the bacterial chemotaxis protein CheY, and other evidence suggests that the adaptors can make heterotypic interactions with both the receptors and themselves. Here we show that the purified TIR domains of Mal and MyD88 can form stable heterodimers and also that Mal homodimers and oligomers are dissociated in the presence of ATP. To identify structural features that may contribute to the formation of signaling complexes, we produced models of the TIR domains from human Toll-like receptor 4 (TLR4), Mal, and MyD88. We found that although the overall fold is conserved the electrostatic surface potentials are quite distinct. Docking studies of the models suggest that Mal and MyD88 bind to different regions in TLRs 2 and 4, a finding consistent with a cooperative role of the two adaptors in signaling. Mal and MyD88 are predicted to interact at a third non-overlapping site, suggesting that the receptor and adaptors may form heterotetrameric complexes. The theoretical model of the interactions is supported by experimental data from glutathione S-transferase pull-downs and co-immunoprecipitations. Neither theoretical nor experimental data suggest a direct role for the conserved proline in the BB-loop in the association of TLR4, Mal, and MyD88. Finally we show a sequence relationship between the Drosophila protein Tube and Mal that may indicate a functional equivalence of these two adaptors in the Drosophila and vertebrate Toll pathways.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. DMPD: Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17667936 Structure, function and regulation of the Toll/IL-1 receptor adaptor prote... (.svg) (.html) (.csml) Show Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. ...PubmedID 17667936 Title Structure, function and regulation of the Toll/IL-1 recep

  9. 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...

  10. Selective autophagy of non-ubiquitylated targets in plants: looking for cognate receptor/adaptor proteins

    Directory of Open Access Journals (Sweden)

    Vasko eVeljanovski

    2014-06-01

    Full Text Available Cellular homeostasis is essential for the physiology of eukaryotic cells. Eukaryotic cells, including plant cells, utilize two main pathways to adjust the level of cytoplasmic components, namely the proteasomal and the lysosomal/vacuolar pathways. Macroautophagy is a lysosomal/vacuolar pathway which, until recently, was thought to be non-specific and a bulk degradation process. However, selective autophagy which can be activated in the cell under various physiological conditions, involves the specific degradation of defined macromolecules or organelles by a conserved molecular mechanism. For this process to be efficient, the mechanisms underlying the recognition and selection of the cargo to be engulfed by the double-membrane autophagosome are critical, and not yet well understood. Ubiquitin (poly-ubiquitin conjugation to the target appears to be a conserved ligand mechanism in many types of selective autophagy, and defined receptors/adaptors recognizing and regulating the autophagosomal capture of the ubiquitylated target have been characterized. However, non-proteinaceous and non-ubiquitylated cargoes are also selectively degraded by this pathway. This ubiquitin-independent selective autophagic pathway also involves receptor and/or adaptor proteins linking the cargo to the autophagic machinery. Some of these receptor/adaptor proteins including accessory autophagy-related (Atg and non-Atg proteins have been described in yeast and animal cells but not yet in plants. In this review we discuss the ubiquitin-independent cargo selection mechanisms in selective autophagy degradation of organelles and macromolecules and speculate on potential plant receptor/adaptor proteins.

  11. 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.

  12. 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...

  13. 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

  14. Interactive roles of Ras, insulin receptor substrate-1, and proteins with Src homology-2 domains in insulin signaling in Xenopus oocytes.

    Science.gov (United States)

    Chuang, L M; Hausdorff, S F; Myers, M G; White, M F; Birnbaum, M J; Kahn, C R

    1994-11-04

    Insulin receptor substrate-1 (IRS-1) serves as the major immediate substrate of insulin/insulin-like growth factor (IGF)-1 receptors and following tyrosine phosphorylation binds to specific Src homology-2 (SH2) domain-containing proteins including the p85 subunit of phosphatidylinositol (PI) 3-kinase and GRB2, a molecule believed to link IRS-1 to the Ras pathway. To investigate how these SH2-containing signaling molecules interact to regulate insulin/IGF-1 action, IRS-1, glutathione S-transferase (GST)-SH2 domain fusion proteins and Ras proteins were microinjected into Xenopus oocytes. We found that pleiotropic insulin actions are mediated by IRS-1 through two independent, but convergent, pathways involving PI 3-kinase and GRB2. Thus, microinjection of GST-fusion proteins of either p85 or GRB2 inhibited IRS-1-dependent activation of mitogen-activated protein (MAP) and S6 kinases and oocyte maturation, although only the GST-SH2 of p85 reduced insulin-stimulated PI 3-kinase activation. Co-injection of a dominant negative Ras (S17N) with IRS-1 inhibited insulin-stimulated MAP and S6 kinase activation. Micro-injection of activated [Arg12,Thr59]Ras increased basal MAP and S6 kinase activities and sensitized the oocytes to insulin-stimulated maturation without altering insulin-stimulated PI 3-kinase. The Ras-enhanced oocyte maturation response, but not the elevated basal level of MAP and S6 kinase, was partially blocked by the SH2-p85, but not SH2-GRB2. These data strongly suggest that IRS-1 can mediate many of insulin's actions on cellular enzyme activation and cell cycle progression requires binding and activation of multiple different SH2-domain proteins.

  15. Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate.

    Science.gov (United States)

    Lee, Young Kwang; Low-Nam, Shalini T; Chung, Jean K; Hansen, Scott D; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T

    2017-04-28

    The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification.

  16. THE SWIFT GRB HOST GALAXY LEGACY SURVEY. II. REST-FRAME NEAR-IR LUMINOSITY DISTRIBUTION AND EVIDENCE FOR A NEAR-SOLAR METALLICITY THRESHOLD

    Energy Technology Data Exchange (ETDEWEB)

    Perley, D. A. [Department of Astronomy, California Institute of Technology, MC 249-17, 1200 East California Blvd., Pasadena, CA 91125 (United States); Tanvir, N. R. [Department of Physics and Astronomy, University of Leicester, University Road, Leicester, LE1 7RH (United Kingdom); Hjorth, J.; Fynbo, J. P. U.; Krühler, T. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 København Ø (Denmark); Laskar, T.; Berger, E. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Chary, R. [US Planck Data Center, MS220-6, Pasadena, CA 91125 (United States); Postigo, A. de Ugarte [Instituto de Astrofísica de Andalucía (IAA-CSIC), Glorieta de la Astronomía s/n, E-18008, Granada (Spain); Levan, A. J. [Department of Physics, University of Warwick, Coventry CV4 7AL (United Kingdom); Michałowski, M. J. [Scottish Universities Physics Alliance, Institute for Astronomy, University of Edinburgh, Royal Observatory, Edinburgh, EH9 3HJ (United Kingdom); Schulze, S., E-mail: dperley@dark-cosmology.dk [Instituto de Astrofísica, Facultad de Física, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, 7820436 Macul, Santiago 22 (Chile)

    2016-01-20

    We present rest-frame near-IR (NIR) luminosities and stellar masses for a large and uniformly selected population of gamma-ray burst (GRB) host galaxies using deep Spitzer Space Telescope imaging of 119 targets from the Swift GRB Host Galaxy Legacy Survey spanning 0.03 < z < 6.3, and we determine the effects of galaxy evolution and chemical enrichment on the mass distribution of the GRB host population across cosmic history. We find a rapid increase in the characteristic NIR host luminosity between z ∼ 0.5 and z ∼ 1.5, but little variation between z ∼ 1.5 and z ∼ 5. Dust-obscured GRBs dominate the massive host population but are only rarely seen associated with low-mass hosts, indicating that massive star-forming galaxies are universally and (to some extent) homogeneously dusty at high redshift while low-mass star-forming galaxies retain little dust in their interstellar medium. Comparing our luminosity distributions with field surveys and measurements of the high-z mass–metallicity relation, our results have good consistency with a model in which the GRB rate per unit star formation is constant in galaxies with gas-phase metallicity below approximately the solar value but heavily suppressed in more metal-rich environments. This model also naturally explains the previously reported “excess” in the GRB rate beyond z ≳ 2; metals stifle GRB production in most galaxies at z < 1.5 but have only minor impact at higher redshifts. The metallicity threshold we infer is much higher than predicted by single-star models and favors a binary progenitor. Our observations also constrain the fraction of cosmic star formation in low-mass galaxies undetectable to Spitzer to be small at z < 4.

  17. 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.

  18. The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation1

    Science.gov (United States)

    Claudio, Estefania; Sønder, Søren Ulrik; Saret, Sun; Carvalho, Gabrielle; Ramalingam, Thirumalai R; Wynn, Thomas A; Chariot, Alain; Garcia-Perganeda, Antonio; Leonardi, Antonio; Paun, Andrea; Chen, Amy; Ren, Nina Y.; Wang, Hongshan; Siebenlist, Ulrich

    2008-01-01

    IL-17 is the signature cytokine of recently discovered T helper type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well as in autoimmune diseases, such as rheumatoid arthritis and experimental autoimmune encephalomyelitis in animal models. IL-25 is a member of the IL-17 family of cytokines, but has been associated with Th2 responses instead and may negatively cross-regulate Th17/IL-17 responses. IL-25 can initiate an allergic asthma-like inflammation in the airways, which includes recruitment of eosinophils, mucus hypersecretion, Th2 cytokine production and airways hyperreactivity. We demonstrate that these effects of IL-25 are entirely dependent on the adaptor protein CIKS (a.k.a. Act1). Surprisingly, this adaptor is necessary to transmit IL-17 signals as well, despite the very distinct biologic responses these two cytokines elicit. We identify CD11c+ macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo. PMID:19155511

  19. 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...

  20. Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C on the regulation of Toll-like receptors, adaptor proteins and inflammatory response

    Directory of Open Access Journals (Sweden)

    Weith Andreas

    2005-11-01

    Full Text Available Abstract Background Bacterial and viral exacerbations play a crucial role in a variety of lung diseases including COPD or asthma. Since the lung epithelium is a major source of various inflammatory mediators that affect the immune response, we analyzed the inflammatory reaction of primary lung epithelial cells to different microbial molecules that are recognized by Toll-like receptors (TLR. Methods The effects of TLR ligands on primary small airway epithelial cells were analyzed in detail with respect to cytokine, chemokine and matrix metalloproteinase secretion. In addition, the regulation of the expression of TLRs and their adaptor proteins in small airway epithelial cells was investigated. Results Our data demonstrate that poly(I:C, a synthetic analog of viral dsRNA, mediated the strongest proinflammatory effects among the tested ligands, including an increased secretion of IL-6, IL-8, TNF-α, GM-CSF, GRO-α, TARC, MCP-1, MIP-3α, RANTES, IFN-β, IP-10 and ITAC as well as an increased release of MMP-1, MMP-8, MMP-9, MMP-10 and MMP-13. Furthermore, our data show that poly(I:C as well as type-1 and type-2 cytokines have a pronounced effect on the expression of TLRs and molecules involved in TLR signaling in small airway epithelial cells. Poly(I:C induced an elevated expression of TLR1, TLR2 and TLR3 and increased the gene expression of the general TLR adaptor MyD88 and IRAK-2. Simultaneously, poly(I:C decreased the expression of TLR5, TLR6 and TOLLIP. Conclusion Poly(I:C, an analog of viral dsRNA and a TLR3 ligand, triggers a strong inflammatory response in small airway epithelial cells that is likely to contribute to viral exacerbations of pulmonary diseases like asthma or COPD. The pronounced effects of poly(I:C on the expression of Toll-like receptors and molecules involved in TLR signaling is assumed to influence the immune response of the lung epithelium to viral and bacterial infections. Likewise, the regulation of TLR expression by type

  1. Design and Calibration of a Dispersive Imaging Spectrometer Adaptor for a Fast IR Camera on NSTX-U

    Science.gov (United States)

    Reksoatmodjo, Richard; Gray, Travis; Princeton Plasma Physics Laboratory Team

    2017-10-01

    A dispersive spectrometer adaptor was designed, constructed and calibrated for use on a fast infrared camera employed to measure temperatures on the lower divertor tiles of the NSTX-U tokamak. This adaptor efficiently and evenly filters and distributes long-wavelength infrared photons between 8.0 and 12.0 microns across the 128x128 pixel detector of the fast IR camera. By determining the width of these separated wavelength bands across the camera detector, and then determining the corresponding average photon count for each photon wavelength, a very accurate measurement of the temperature, and thus heat flux, of the divertor tiles can be calculated using Plank's law. This approach of designing an exterior dispersive adaptor for the fast IR camera allows accurate temperature measurements to be made of materials with unknown emissivity. Further, the relative simplicity and affordability of this adaptor design provides an attractive option over more expensive, slower, dispersive IR camera systems. This work was made possible by funding from the Department of Energy for the Summer Undergraduate Laboratory Internship (SULI) program. This work is supported by the US DOE Contract No. DE-AC02-09CH11466.

  2. 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...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.

    Science.gov (United States)

    Raabe, T; Olivier, J P; Dickson, B; Liu, X; Gish, G D; Pawson, T; Hafen, E

    1995-06-01

    The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. We have used a combined biochemical and genetic approach to study the interactions between Sev, Drk and Sos. We show that Tyr2546 in the cytoplasmic tail of Sev is required for Drk binding, probably because it provides a recognition site for the Drk SH2 domain. Interestingly, a mutation at this site does not completely block Sev function in vivo. This may suggest that Sev can signal in a Drk-independent, parallel pathway or that Drk can also bind to an intermediate docking protein. Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. We show that the N-terminal Drk SH3 domain is primarily responsible for binding to the tail of Sos in vitro, and for signalling to Ras in vivo.

  10. SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export.

    Science.gov (United States)

    Müller-McNicoll, Michaela; Botti, Valentina; de Jesus Domingues, Antonio M; Brandl, Holger; Schwich, Oliver D; Steiner, Michaela C; Curk, Tomaz; Poser, Ina; Zarnack, Kathi; Neugebauer, Karla M

    2016-03-01

    Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that couple pre-mRNA processing to mRNA export. Consistent with this proposal, >1000 endogenous mRNAs required individual SR proteins for nuclear export in vivo. To address the mechanism, transcriptome-wide RNA-binding profiles of NXF1 and SRSF1-7 were determined in parallel by individual-nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP). Quantitative comparisons of RNA-binding sites showed that NXF1 and SR proteins bind mRNA targets at adjacent sites, indicative of cobinding. SRSF3 emerged as the most potent NXF1 adaptor, conferring sequence specificity to RNA binding by NXF1 in last exons. Interestingly, SRSF3 and SRSF7 were shown to bind different sites in last exons and regulate 3' untranslated region length in an opposing manner. Both SRSF3 and SRSF7 promoted NXF1 recruitment to mRNA. Thus, SRSF3 and SRSF7 couple alternative splicing and polyadenylation to NXF1-mediated mRNA export, thereby controlling the cytoplasmic abundance of transcripts with alternative 3' ends. © 2016 Müller-McNicoll et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Manufacturing and QA of adaptors for LHC

    International Nuclear Information System (INIS)

    Madhu Murthy, V.; Dwivedi, J.; Goswami, S.G.; Soni, H.C.; Mainaud Durand, H.; Quesnel, J.P.; )

    2006-01-01

    The LHC low beta quadrupoles, have very tight alignment tolerances and are located in areas with strong radiation field. They require remote re-alignment, by motorized jacks, based on the feedback of alignment sensors of each magnet. Jacks designed to support arc cryomagnets of LHC are modified and motorized with the help of adaptors. Two types of adapters, for vertical and transverse axes of the jacks, were developed and supplied through collaboration between RRCAT, DAE, India and CERN, Geneva. This paper describes their functional requirements, manufacture and quality assurance (QA). (author)

  12. 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.

  13. 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.

  14. 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

  15. 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.

  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. 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.

  18. 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.

  19. 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.

  20. 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

  1. Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive organ development in Arabidopsis.

    Science.gov (United States)

    Kim, Soo Youn; Xu, Zheng-Yi; Song, Kyungyoung; Kim, Dae Heon; Kang, Hyangju; Reichardt, Ilka; Sohn, Eun Ju; Friml, Jirí; Juergens, Gerd; Hwang, Inhwan

    2013-08-01

    Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.

  2. 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.

  3. The p66(Shc adaptor protein controls oxidative stress response in early bovine embryos.

    Directory of Open Access Journals (Sweden)

    Dean H Betts

    Full Text Available The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, including mitochondrial ROS generation and the repression of antioxidant gene expression. We have previously demonstrated a strong relationship with elevated p66Shc levels, reduced antioxidant levels and greater intracellular ROS generation with the high incidence of permanent cell cycle arrest of 2-4 cell embryos cultured under high oxygen tensions or after oxidant treatment. The main objective of this study was to establish a functional role for p66Shc in regulating the oxidative stress response during early embryo development. Using RNA interference in bovine zygotes we show that p66Shc knockdown embryos exhibited increased MnSOD levels, reduced intracellular ROS and DNA damage that resulted in a greater propensity for development to the blastocyst stage. P66Shc knockdown embryos were stress resistant exhibiting significantly reduced intracellular ROS levels, DNA damage, permanent 2-4 cell embryo arrest and diminished apoptosis frequencies after oxidant treatment. The results of this study demonstrate that p66Shc controls the oxidative stress response in early mammalian embryos. Small molecule inhibition of p66Shc may be a viable clinical therapy to increase the developmental potential of in vitro produced mammalian embryos.

  4. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    Directory of Open Access Journals (Sweden)

    Wei Sheng Chia

    Full Text Available p97/Valosin-containing protein (VCP is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD. It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  5. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    Science.gov (United States)

    Chia, Wei Sheng; Chia, Diana Xueqi; Rao, Feng; Bar Nun, Shoshana; Geifman Shochat, Susana

    2012-01-01

    p97/Valosin-containing protein (VCP) is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD). It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  6. 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.

  7. 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.

  8. Polarimetry and Photometry of Gamma-Ray Bursts with RINGO2

    Science.gov (United States)

    Steele, I. A.; Kopač, D.; Arnold, D. M.; Smith, R. J.; Kobayashi, S.; Jermak, H. E.; Mundell, C. G.; Gomboc, A.; Guidorzi, C.; Melandri, A.; Japelj, J.

    2017-07-01

    We present a catalog of early-time (˜ {10}2-{10}4 s) photometry and polarimetry of all gamma-ray burst (GRB) optical afterglows observed with the RINGO2 imaging polarimeter on the Liverpool Telescope. Of the 19 optical afterglows observed, the following nine were bright enough to perform photometry and attempt polarimetry: GRB 100805A, GRB 101112A, GRB 110205A, GRB 110726A, GRB 120119A, GRB 120308A, GRB 120311A, GRB 120326A, and GRB 120327A. We present multiwavelength light curves for these 9 GRBs, together with estimates of their optical polarization degrees and/or limits. We carry out a thorough investigation of detection probabilities, instrumental properties, and systematics. Using two independent methods, we confirm previous reports of significant polarization in GRB 110205A and 120308A, and report the new detection of P={6}-2+3% in GRB101112A. We discuss the results for the sample in the context of the reverse- and forward-shock afterglow scenario, and show that GRBs with detectable optical polarization at early time have clearly identifiable signatures of reverse-shock emission in their optical light curves. This supports the idea that GRB ejecta contain large-scale magnetic fields, and it highlights the importance of rapid-response polarimetry.

  9. 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.

  10. The adaptor protein SAP directly associates with PECAM-1 and regulates PECAM-1-mediated-cell adhesion in T-like cell lines.

    Science.gov (United States)

    Proust, Richard; Crouin, Catherine; Gandji, Leslie Yewakon; Bertoglio, Jacques; Gesbert, Franck

    2014-04-01

    SAP is a small cytosolic adaptor protein expressed in hematopoietic lineages whose main function is to regulate intracellular signaling pathways induced by the triggering of members of the SLAM receptor family. In this paper, we have identified the adhesion molecule PECAM-1 as a new partner for SAP in a conditional yeast two-hybrid screen. PECAM-1 is an immunoglobulin-like molecule expressed by endothelial cells and leukocytes, which possesses both pro- and anti-inflammatory properties. However, little is known about PECAM-1 functions in T cells. We show that SAP directly and specifically interacts with the cytosolic tyrosine 686 of PECAM-1. We generated different T-like cell lines in which SAP or PECAM-1 are expressed or down modulated and we demonstrate that a diminished SAP expression correlates with a diminished PECAM-1-mediated adhesion. Although SAP has mainly been shown to associate with SLAM receptors, we evidence here that SAP is a new actor downstream of PECAM-1. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. 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.

  12. 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

  13. 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.

  14. 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).

  15. 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

  16. 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

  17. Polarimetric Analysis of the Long Duration Gamma-Ray Burst GRB 160530A With the Balloon Borne Compton Spectrometer and Imager

    Energy Technology Data Exchange (ETDEWEB)

    Lowell, A. W.; Boggs, S. E; Chiu, C. L.; Kierans, C. A.; Sleator, C.; Tomsick, J. A.; Zoglauer, A. C. [Space Sciences Laboratory, University of California, Berkeley (United States); Chang, H.-K.; Tseng, C.-H.; Yang, C.-Y. [Institute of Astronomy, National Tsing Hua University, Taiwan (China); Jean, P.; Ballmoos, P. von [IRAP Toulouse (France); Lin, C.-H. [Institute of Physics, Academia Sinica, Taiwan (China); Amman, M. [Lawrence Berkeley National Laboratory (United States)

    2017-10-20

    A long duration gamma-ray burst, GRB 160530A, was detected by the Compton Spectrometer and Imager (COSI) during the 2016 COSI Super Pressure Balloon campaign. As a Compton telescope, COSI is inherently sensitive to the polarization of gamma-ray sources in the energy range 0.2–5.0 MeV. We measured the polarization of GRB 160530A using (1) a standard method (SM) based on fitting the distribution of azimuthal scattering angles with a modulation curve and (2) an unbinned, maximum likelihood method (MLM). In both cases, the measured polarization level was below the 99% confidence minimum detectable polarization levels of 72.3% ± 0.8% (SM) and 57.5% ± 0.8% (MLM). Therefore, COSI did not detect polarized gamma-ray emission from this burst. Our most constraining 90% confidence upper limit on the polarization level was 46% (MLM).

  18. The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond

    Directory of Open Access Journals (Sweden)

    Fubito Nakatsu

    2014-11-01

    Full Text Available The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane. Adaptor protein (AP-1, a member of the AP complex family, which includes the ubiquitously expressed AP-1A and the epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network and/or at the recycling endosomes. A growing body of evidence, especially from studies using model organisms and animals, demonstrates that the AP-1-mediated polarized sorting supports the development and physiology of multi-cellular units as functional organs and tissues (e.g., cell fate determination, inflammation and gut immune homeostasis. Furthermore, a possible involvement of AP-1B in the pathogenesis of human diseases, such as Crohn’s disease and cancer, is now becoming evident. These data highlight the significant contribution of AP-1 complexes to the physiology of multicellular organisms, as master regulators of polarized sorting in epithelial cells.

  19. GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells.

    Science.gov (United States)

    Bilal, Mahmood Y; Zhang, Elizabeth Y; Dinkel, Brittney; Hardy, Daimon; Yankee, Thomas M; Houtman, Jon C D

    2015-04-01

    GRB2 related adaptor protein downstream of Shc (GADS) is a member of the GRB2 family of adaptors and is critical for TCR-induced signaling. The current model is that GADS recruits SLP-76 to the LAT complex, which facilitates the phosphorylation of SLP-76, the activation of PLC-γ1, T cell adhesion and cytokine production. However, this model is largely based on studies of disruption of the GADS/SLP-76 interaction and murine T cell differentiation in GADS deficient mice. The role of GADS in mediating TCR-induced signals in human CD4+ T cells has not been thoroughly investigated. In this study, we have suppressed the expression of GADS in human CD4+ HuT78 T cells. GADS deficient HuT78 T cells displayed similar levels of TCR-induced SLP-76 and PLC-γ1 phosphorylation but exhibited substantial decrease in TCR-induced IL-2 and IFN-γ release. The defect in cytokine production occurred because of impaired calcium mobilization due to reduced recruitment of SLP-76 and PLC-γ1 to the LAT complex. Surprisingly, both GADS deficient HuT78 and GADS deficient primary murine CD8+ T cells had similar TCR-induced adhesion when compared to control T cells. Overall, our results show that GADS is required for calcium influx and cytokine production, but not cellular adhesion, in human CD4+ T cells, suggesting that the current model for T cell regulation by GADS is incomplete. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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

  1. 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

  2. Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells.

    Science.gov (United States)

    Schaletzki, Yvonne; Kromrey, Marie-Luise; Bröderdorf, Susanne; Hammer, Elke; Grube, Markus; Hagen, Paul; Sucic, Sonja; Freissmuth, Michael; Völker, Uwe; Greinacher, Andreas; Rauch, Bernhard H; Kroemer, Heyo K; Jedlitschky, Gabriele

    2017-01-05

    The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter. We approached this issue by searching for interacting proteins by in vitro binding assays, followed by immunoblotting and mass spectrometry, and by visualising their co-localisation in platelets and haematopoietic cells. We identified the PDZ domain containing scaffold proteins ezrin-binding protein 50 (EBP50/NHERF1), postsynaptic density protein 95 (PSD95), and sorting nexin 27 (SNX27), but also the adaptor protein complex 3 subunit β3A (AP3B1) and the heat shock protein HSP90 as putative interaction partners of MRP4. The knock-down of SNX27, PSD95, and AP3B1 by siRNA in megakaryoblastic leukaemia cells led to a redistribution of MRP4 from intracellular structures to the plasma membrane. Inhibition of HSP90 led to a diminished expression and retention of MRP4 in the endoplasmic reticulum. These results indicate that MRP4 localisation and function are regulated by multiple protein interactions. Changes in the adaptor proteins can hence lead to altered localisation and function of the transporter.

  3. 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.

  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. Gas inflow and outflow in an interacting high-redshift galaxy. The remarkable host environment of GRB 080810 at z = 3.35

    Science.gov (United States)

    Wiseman, P.; Perley, D. A.; Schady, P.; Prochaska, J. X.; de Ugarte Postigo, A.; Krühler, T.; Yates, R. M.; Greiner, J.

    2017-11-01

    We reveal multiple components of an interacting galaxy system at z ≈ 3.35 through a detailed analysis of the exquisite high-resolution Keck/HIRES spectrum of the afterglow of a gamma-ray burst (GRB). Through Voigt-profile fitting of absorption lines from the Lyman series, we constrain the neutral hydrogen column density to NH I ≤ 1018.35 cm-2 for the densest of four distinct systems at the host redshift of GRB 080810, which is among the lowest NH I ever observed in a GRB host, even though the line of sight passes within a projected 5 kpc of the galaxy centres. By detailed analysis of the corresponding metal absorption lines, we derive chemical, ionic, and kinematic properties of the individual absorbing systems, and thus build a picture of the host as a whole. Striking differences between the systems imply that the line of sight passes through several phases of gas: the star-forming regions of the GRB host; enriched material in the form of a galactic outflow; the hot and ionised halo of a second interacting galaxy falling towards the host at a line-of-sight velocity of 700 km s-1; and a cool metal-poor cloud that may represent one of the best candidates yet for the inflow of metal-poor gas from the intergalactic medium. The reduced spectrum 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/A107

  6. 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

  7. 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.

  8. Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer

    National Research Council Canada - National Science Library

    Fathers, Kelly E

    2007-01-01

    The Crk adaptor proteins (CrkI, CrkII and CrkL) play an important role during cellular signalling by mediating the formation of protein-protein complexes and are involved in cellular migration, invasion, and adhesion...

  9. Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer

    National Research Council Canada - National Science Library

    Fathers, Kelly E

    2008-01-01

    The Crk adaptor proteins (CrkI, CrkII and CrkL) play an important role during cellular signalling by mediating the formation of protein-protein complexes and are involved in cellular migration, invasion, and adhesion...

  10. Conformational changes in the AAA ATPase p97–p47 adaptor complex

    Science.gov (United States)

    Beuron, Fabienne; Dreveny, Ingrid; Yuan, Xuemei; Pye, Valerie E; Mckeown, Ciaran; Briggs, Louise C; Cliff, Matthew J; Kaneko, Yayoi; Wallis, Russell; Isaacson, Rivka L; Ladbury, John E; Matthews, Steve J; Kondo, Hisao; Zhang, Xiaodong; Freemont, Paul S

    2006-01-01

    The AAA+ATPase p97/VCP, helped by adaptor proteins, exerts its essential role in cellular events such as endoplasmic reticulum-associated protein degradation or the reassembly of Golgi, ER and the nuclear envelope after mitosis. Here, we report the three-dimensional cryo-electron microscopy structures at ∼20 Å resolution in two nucleotide states of the endogenous hexameric p97 in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins involved in membrane fusion. Depending on the nucleotide state, we observe the p47 trimer to be in two distinct arrangements on top of the p97 hexamer. By combining the EM data with NMR and other biophysical measurements, we propose a model of ATP-dependent p97(N) domain motions that lead to a rearrangement of p47 domains, which could result in the disassembly of target protein complexes. PMID:16601695

  11. A Search for gravitational waves associated with the gamma ray burst GRB030329 using the LIGO detectors

    Energy Technology Data Exchange (ETDEWEB)

    Abbott, B.; Abbott, R.; Adhikari, R.; Ageev, A.; Allen, B.; Amin, R.; Anderson, S.B.; Anderson, W.G.; Araya, M.; Armandula, H.; Ashley, M.; Asiri, F.; Aufmuth, P.; Aulbert, C.; Babak, S.; Balasubramanian, R.; Ballmer, S.; Barish, B.C.; Barker, C.; Barker, D.; Barnes, M.; /Potsdam, Max Planck Inst. /Hannover, Max Planck Inst. Grav. /Australian

    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 {approx_equal}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 pre-determined threshold. We report frequency dependent upper limits on the strength of the gravitational waves associated with GRB030329. Near the most sensitive frequency region, around {approx_equal}250 Hz, our root-sum-square (RSS) gravitational wave strain sensitivity for optimally polarized bursts was better than h{sub RSS} {approx_equal} 6 x 10{sup -21} Hz{sup -1/2}. Our result is comparable to the best published results searching for association between gravitational waves and GRBs.

  12. Estimating detection rates for the LIGO-Virgo search for gravitational-wave burst counterparts to gamma-ray bursts using inferred local GRB rates

    International Nuclear Information System (INIS)

    Leonor, I; Frey, R; Sutton, P J; Jones, G; Marka, S; Marka, Z

    2009-01-01

    One of the ongoing searches performed using the LIGO-Virgo network of gravitational-wave interferometers is the search for gravitational-wave burst (GWB) counterparts to gamma-ray bursts (GRBs). This type of analysis makes use of GRB time and position information from gamma-ray satellite detectors to trigger the GWB search, and the GWB detection rates possible for such an analysis thus strongly depend on the GRB detection efficiencies of the satellite detectors. Using local GRB rate densities inferred from observations which are found in the science literature, we calculate estimates of the GWB detection rates for different configurations of the LIGO-Virgo network for this type of analysis.

  13. 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

  14. CEACAM3-mediated phagocytosis of human-specific bacterial pathogens involves the adaptor molecule Nck

    OpenAIRE

    Peterson, Lisa

    2010-01-01

    Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are exploited by human-specific pathogens to anchor themselves to or invade host cells. Interestingly, human granulocytes express a specific isoform, CEACAM3, that can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella and Haemophilus species. As opsonin-independent phagocytosis of CEACAM-binding Neisseria depends on Src-family protein tyrosine kinase (PTK) phosphorylation of the CEACAM3 ...

  15. 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).

  16. 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

  17. Origins and Early Evolution of the tRNA Molecule

    Directory of Open Access Journals (Sweden)

    Koji Tamura

    2015-12-01

    Full Text Available Modern transfer RNAs (tRNAs are composed of ~76 nucleotides and play an important role as “adaptor” molecules that mediate the translation of information from messenger RNAs (mRNAs. Many studies suggest that the contemporary full-length tRNA was formed by the ligation of half-sized hairpin-like RNAs. A minihelix (a coaxial stack of the acceptor stem on the T-stem of tRNA can function both in aminoacylation by aminoacyl tRNA synthetases and in peptide bond formation on the ribosome, indicating that it may be a vestige of the ancestral tRNA. The universal CCA-3′ terminus of tRNA is also a typical characteristic of the molecule. “Why CCA?” is the fundamental unanswered question, but several findings give a comprehensive picture of its origin. Here, the origins and early evolution of tRNA are discussed in terms of various perspectives, including nucleotide ligation, chiral selectivity of amino acids, genetic code evolution, and the organization of the ribosomal peptidyl transferase center (PTC. The proto-tRNA molecules may have evolved not only as adaptors but also as contributors to the composition of the ribosome.

  18. Adaptor Protein Complex 2–Mediated Endocytosis Is Crucial for Male Reproductive Organ Development in Arabidopsis[W

    Science.gov (United States)

    Kim, Soo Youn; Xu, Zheng-Yi; Song, Kyungyoung; Kim, Dae Heon; Kang, Hyangju; Reichardt, Ilka; Sohn, Eun Ju; Friml, Jiří; Juergens, Gerd; Hwang, Inhwan

    2013-01-01

    Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2–dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs. PMID:23975898

  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. Positron-Electron Annihilation Process in (2,2)-Difluoropropane Molecule

    Science.gov (United States)

    Liu, Yang; Ma, Xiao-Guang; Zhu, Ying-Hao

    2016-04-01

    The positron-electron annihilation process in (2,2)-difluoropropane molecule and the corresponding gamma-ray spectra are studied by quantum chemistry method. The positrophilic electrons in (2,2)-difluoropropane molecule are found for the first time. The theoretical predictions show that the outermost 2s electrons of fluoride atoms play an important role in positron-electron annihilation process of (2,2)-difiuoropropane. In the present scheme, the correlation coefficient between the theoretical gamma-ray spectra and the experiments can be 99%. The present study gives an alternative annihilation model for positron-electron pair in larger molecules. Supported by the National Natural Science Foundation of China under Grant No. 11347011 and the Natural Science Foundation Project of Shandong Province under Grant No. ZR2011AM010 and 2014 Technology Innovation Fund of Ludong University under Grant Nos. 1d151007 and ld15l016

  1. 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)

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. NTAL (non-T cell activation linker):a transmembrane adaptor protein involved in immunoreceptor signaling

    Czech Academy of Sciences Publication Activity Database

    Brdička, Tomáš; Imrich, Martin; Angelisová, Pavla; Brdičková, Naděžda; Horváth, Ondřej; Špička, Jiří; Hilgert, Ivan; Lusková, Petra; Dráber, Petr; Novák, P.; Engels, N.; Wienands, J.; Simeoni, L.; Osterreicher, J.; Aguado, E.; Malissen, M.; Schraven, B.; Hořejší, Václav

    2002-01-01

    Roč. 196, č. 12 (2002), s. 16180-16185 ISSN 0022-1007 R&D Projects: GA MŠk LN00A026 Keywords : NTAL * transmembrane adaptor * immunoreceptor signaling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 15.838, year: 2002

  7. 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

  8. 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.

  9. Tetraspanins and Transmembrane Adaptor Proteins As Plasma Membrane Organizers-Mast Cell Case.

    Science.gov (United States)

    Halova, Ivana; Draber, Petr

    2016-01-01

    The plasma membrane contains diverse and specialized membrane domains, which include tetraspanin-enriched domains (TEMs) and transmembrane adaptor protein (TRAP)-enriched domains. Recent biophysical, microscopic, and functional studies indicated that TEMs and TRAP-enriched domains are involved in compartmentalization of physicochemical events of such important processes as immunoreceptor signal transduction and chemotaxis. Moreover, there is evidence of a cross-talk between TEMs and TRAP-enriched domains. In this review we discuss the presence and function of such domains and their crosstalk using mast cells as a model. The combined data based on analysis of selected mast cell-expressed tetraspanins [cluster of differentiation (CD)9, CD53, CD63, CD81, CD151)] or TRAPs [linker for activation of T cells (LAT), non-T cell activation linker (NTAL), and phosphoprotein associated with glycosphingolipid-enriched membrane microdomains (PAG)] using knockout mice or specific antibodies point to a diversity within these two families and bring evidence of the important roles of these molecules in signaling events. An example of this diversity is physical separation of two TRAPs, LAT and NTAL, which are in many aspects similar but show plasma membrane location in different microdomains in both non-activated and activated cells. Although our understanding of TEMs and TRAP-enriched domains is far from complete, pharmaceutical applications of the knowledge about these domains are under way.

  10. 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.

  11. 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

  12. 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...

  13. 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,

  14. 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.

  15. 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.

  16. 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....

  17. A low-latency pipeline for GRB light curve and spectrum using Fermi/GBM near real-time data

    Science.gov (United States)

    Zhao, Yi; Zhang, Bin-Bin; Xiong, Shao-Lin; Long, Xi; Zhang, Qiang; Song, Li-Ming; Sun, Jian-Chao; Wang, Yuan-Hao; Li, Han-Cheng; Bu, Qing-Cui; Feng, Min-Zi; Li, Zheng-Heng; Wen, Xing; Wu, Bo-Bing; Zhang, Lai-Yu; Zhang, Yong-Jie; Zhang, Shuang-Nan; Shao, Jian-Xiong

    2018-05-01

    Rapid response and short time latency are very important for Time Domain Astronomy, such as the observations of Gamma-ray Bursts (GRBs) and electromagnetic (EM) counterparts of gravitational waves (GWs). Based on near real-time Fermi/GBM data, we developed a low-latency pipeline to automatically calculate the temporal and spectral properties of GRBs. With this pipeline, some important parameters can be obtained, such as T 90 and fluence, within ∼ 20 min after the GRB trigger. For ∼ 90% of GRBs, T 90 and fluence are consistent with the GBM catalog results within 2σ errors. This pipeline has been used by the Gamma-ray Bursts Polarimeter (POLAR) and the Insight Hard X-ray Modulation Telescope (Insight-HXMT) to follow up the bursts of interest. For GRB 170817A, the first EM counterpart of GW events detected by Fermi/GBM and INTEGRAL/SPI-ACS, the pipeline gave T 90 and spectral information 21 min after the GBM trigger, providing important information for POLAR and Insight-HXMT observations.

  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. 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

  20. Molecules in strong laser fields. In depth study of H2 molecule

    International Nuclear Information System (INIS)

    Awasthi, Manohar

    2009-01-01

    A method for solving the time-dependent Schroedinger equation (TDSE) describing the electronic motion of the molecules exposed to very short intense laser pulses has been developed. The time-dependent electronic wavefunction is expanded in terms of a superposition of field-free eigenstates. The field-free eigenstates are calculated in two ways. In the first approach, which is applicable to two electron systems like H 2 , fully correlated field-free eigenstates are obtained in complete dimensionality using configuration-interaction calculation where the one-electron basis functions are built from B splines. In the second approach, which is even applicable to larger molecules, the field-free eigenstates are calculated within the single-active-electron (SAE) approximation using density functional theory. In general, the method can be divided into two parts, in the first part the field-free eigenstates are calculated and then in the second part a time propagation for the laser pulse parameters is performed. The H 2 molecule is the testing ground for the implementation of both the methods. The reliability of the configuration interaction (CI) based method for the solution of TDSE (CI-TDSE) is tested by comparing results in the low-intensity regime to the prediction of lowest-order perturbation theory. Another test for the CI-TDSE method is in the united atom limit for the H 2 molecule. By selecting a very small value of the internuclear distance close to zero for the H 2 molecule, Helium atom is obtained. Once the functionality and the reliability of the method is established, it is used for obtaining accurate results for molecular hydrogen exposed to intense laser fields. The results for the standard 800 nm Titanium-Sapphire laser and its harmonics at 400 nm and 266 nm are shown. The results for a scan over a wide range of incident photon energies as well as dependence on the internuclear distance are presented. The photoelectron spectra including above

  1. Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish.

    NARCIS (Netherlands)

    Meijer, A.H.; Krens, SF Gabby; Rodriguez, IA Medina; He, S; Bitter, W.; Snaar-Jagalska, B Ewa; Spaink, H.P.

    2004-01-01

    The zebrafish genomic sequence database was analysed for the presence of genes encoding members of the Toll-like receptors (TLR) and interleukin receptors (IL-R) and associated adaptor proteins containing a TIR domain. The resulting predictions show the presence of one or more counterparts for the

  2. SCIMP, a transmembrane adaptor protein involved in major histocompatibility complex class II signaling

    Czech Academy of Sciences Publication Activity Database

    Dráber, Peter; Vonková, Ivana; Štěpánek, Ondřej; Hrdinka, Matouš; Kucová, Markéta; Skopcová, Tereza; Otáhal, Pavel; Angelisová, Pavla; Hořejší, Václav; Yeung, M.; Weiss, A.; Brdička, Tomáš

    2011-01-01

    Roč. 31, č. 22 (2011), s. 4550-4562 ISSN 0270-7306 R&D Projects: GA MŠk 1M0506; GA ČR GEMEM/09/E011 Institutional research plan: CEZ:AV0Z50520514 Keywords : SCIMP * transmembrane adaptor protein * MHC II Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.527, year: 2011

  3. Brucella TIR-like protein TcpB/Btp1 specifically targets the host adaptor protein MAL/TIRAP to promote infection.

    Science.gov (United States)

    Li, Wenna; Ke, Yuehua; Wang, Yufei; Yang, Mingjuan; Gao, Junguang; Zhan, Shaoxia; Xinying, Du; Huang, Liuyu; Li, Wenfeng; Chen, Zeliang; Li, Juan

    2016-08-26

    Brucella spp. are known to avoid host immune recognition and weaken the immune response to infection. Brucella like accomplish this by employing two clever strategies, called the stealth strategy and hijacking strategy. The TIR domain-containing protein (TcpB/Btp1) of Brucella melitensis is thought to be involved in inhibiting host NF-κB activation by binding to adaptors downstream of Toll-like receptors. However, of the five TIR domain-containing adaptors conserved in mammals, whether MyD88 or MAL, even other three adaptors, are specifically targeted by TcpB has not been identified. Here, we confirmed the effect of TcpB on B.melitensis virulence in mice and found that TcpB selectively targets MAL. By using siRNA against MAL, we found that TcpB from B.melitensis is involved in intracellular survival and that MAL affects intracellular replication of B.melitensis. Our results confirm that TcpB specifically targets MAL/TIRAP to disrupt downstream signaling pathways and promote intra-host survival of Brucella spp. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Time evolution of the spectral break in the high-energy extra component of GRB 090926A

    Science.gov (United States)

    Yassine, M.; Piron, F.; Mochkovitch, R.; Daigne, F.

    2017-10-01

    Aims: The prompt light curve of the long GRB 090926A reveals a short pulse 10 s after the beginning of the burst emission, which has been observed by the Fermi observatory from the keV to the GeV energy domain. During this bright spike, the high-energy emission from GRB 090926A underwent a sudden hardening above 10 MeV in the form of an additional power-law component exhibiting a spectral attenuation at a few hundreds of MeV. This high-energy break has been previously interpreted in terms of gamma-ray opacity to pair creation and has been used to estimate the bulk Lorentz factor of the outflow. In this article, we report on a new time-resolved analysis of the GRB 090926A broadband spectrum during its prompt phase and on its interpretation in the framework of prompt emission models. Methods: We characterized the emission from GRB 090926A at the highest energies with Pass 8 data from the Fermi Large Area Telescope (LAT), which offer a greater sensitivity than any data set used in previous studies of this burst, particularly in the 30-100 MeV energy band. Then, we combined the LAT data with the Fermi Gamma-ray Burst Monitor (GBM) in joint spectral fits to characterize the time evolution of the broadband spectrum from keV to GeV energies. We paid careful attention to the systematic effects that arise from the uncertainties on the LAT response. Finally, we performed a temporal analysis of the light curves and we computed the variability timescales from keV to GeV energies during and after the bright spike. Results: Our analysis confirms and better constrains the spectral break, which has been previously reported during the bright spike. Furthermore, it reveals that the spectral attenuation persists at later times with an increase of the break characteristic energy up to the GeV domain until the end of the prompt phase. We discuss these results in terms of keV-MeV synchroton radiation of electrons accelerated during the dissipation of the jet energy and inverse Compton

  5. 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.

  6. 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.

  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. Type 2 Diabetes Risk Alleles Near BCAR1 and in ANK1 Associate With Decreased ß-Cell Function Whereas Risk Alleles Near ANKRD55 and GRB14 Associate With Decreased Insulin Sensitivity in the Danish Inter99 Cohort

    DEFF Research Database (Denmark)

    Harder, Marie N; Ribel-Madsen, Rasmus; Justesen, Johanne M

    2013-01-01

    Context:Recently, 10 novel type 2 diabetes (T2D) susceptibility single nucleotide polymorphisms (SNPs) in ZMIZ1, ANK1, KLHDC5, TLE1, ANKRD55, CILP2, MC4R, BCAR1, HMG20A, and GRB14 loci were discovered in MetaboChip-genotyped populations of European ancestry.Objective:The aim of the present study ...

  9. Tetraspanins and Transmembrane Adaptor Proteins as Plasma Membrane Organizers – Mast Cell Case

    Directory of Open Access Journals (Sweden)

    Ivana eHalova

    2016-05-01

    Full Text Available The plasma membrane contains diverse and specialized membrane domains, which include tetraspanin-enriched domains (TEMs and transmembrane adaptor protein (TRAP-enriched domains. Recent biophysical, microscopic and functional studies indicated that TEMs and TRAP-enriched domains are involved in compartmentalization of physicochemical events of such important processes as immunoreceptor signal transduction and chemotaxis. Moreover, there is evidence of a cross-talk between TEMs and TRAP-enriched domains. In this review we discuss the presence and function of such domains and their crosstalk using mast cells as a model. The combined data based on analysis of selected mast cell-expressed tetraspanins [cluster of differentiation (CD9, CD53, CD63, CD81, CD151] or TRAPs [linker for activation of T cells (LAT, non-T cell activation linker (NTAL, and phosphoprotein associated with glycosphingolipid-enriched membrane microdomains (PAG] using knockout mice or specific antibodies point to a diversity within these two families and bring evidence of the important roles of these molecules in signaling events. An example of this diversity is physical separation of two TRAPs, LAT and NTAL, which are in many aspects similar but show plasma membrane location in different microdomains in both non-activated and activated cells. Although our understanding of TEMs and TRAP-enriched domains is far from complete, pharmaceutical applications of the knowledge about these domains are under way.

  10. Localization of the kinesin adaptor proteins trafficking kinesin proteins 1 and 2 in primary cultures of hippocampal pyramidal and cortical neurons.

    Science.gov (United States)

    Loss, Omar; Stephenson, F Anne

    2015-07-01

    Neuronal function requires regulated anterograde and retrograde trafficking of mitochondria along microtubules by using the molecular motors kinesin and dynein. Previous work has established that trafficking kinesin proteins (TRAKs),TRAK1 and TRAK2, are kinesin adaptor proteins that link mitochondria to kinesin motor proteins via an acceptor protein in the mitochondrial outer membrane, etc. the Rho GTPase Miro. Recent studies have shown that TRAK1 preferentially controls mitochondrial transport in axons of hippocampal neurons by virtue of its binding to both kinesin and dynein motor proteins, whereas TRAK2 controls mitochondrial transport in dendrites resulting from its binding to dynein. This study further investigates the subcellular localization of TRAK1 and TRAK2 in primary cultures of hippocampal and cortical neurons by using both commercial antibodies and anti-TRAK1 and anti-TRAK2 antibodies raised in our own laboratory (in-house). Whereas TRAK1 was prevalently localized in axons of hippocampal and cortical neurons, TRAK2 was more prevalent in dendrites of hippocampal neurons. In cortical neurons, TRAK2 was equally distributed between axons and dendrites. Some qualitative differences were observed between commercial and in-house-generated antibody immunostaining. © 2015 Wiley Periodicals, Inc.

  11. 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...

  12. 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.

  13. The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling.

    Science.gov (United States)

    Beitner-Johnson, D; Blakesley, V A; Shen-Orr, Z; Jimenez, M; Stannard, B; Wang, L M; Pierce, J; LeRoith, D

    1996-04-19

    The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein which we have previously shown to become rapidly tyrosine phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) in NIH-3T3 cells. In order to further characterize the role of Crk in the IGF-I signaling pathway, NIH-3T3 and 293 cells were stably transfected with an expression vector containing the Crk cDNA. The various resultant 3T3-Crk clones expressed Crk at approximately 2-15-fold higher levels than parental 3T3 cells. In 3T3-Crk cells, Crk immunoreactivity was detected in insulin receptor substrate-1 (IRS-1) immunoprecipitates. Stimulation with IGF-I resulted in a dissociation of Crk protein from IRS-1. In contrast, the association of the related adaptor protein Grb2 with IRS-1 was enhanced by IGF-I stimulation. Similar results were obtained in stably transfected 293-Crk cells, which express both IRS-1 and the IRS-1-related signaling protein 4PS. In these cells, IRS-1 and 4PS both associated with Crk, and this association was also decreased by IGF-I treatment, whereas the association of Grb2 with IRS-1 and 4PS was enhanced by IGF-I. Overexpression of Crk also enhanced IGF-I-induced mitogenesis of NIH-3T3 cells, as measured by [3H]thymidine incorporation. The levels of IGF-I-induced mitogenesis were proportional to the level of Crk expression. These results suggest that Crk is a positive effector of IGF-I signaling, and may mediate its effects via interaction with IRS-1 and/or 4PS.

  14. 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.

  15. Anomalous absorption in H2CN and CH2CN molecules

    Indian Academy of Sciences (India)

    Abstract. Structures of H2CN and CH2CN molecules are similar to that of H2CO mole- cule. The H2CO has shown anomalous absorption for its transition 111 − 110 at 4.8 GHz in a number of cool molecular clouds. Though the molecules H2CN and CH2CN have been identified in TMC-1 and Sgr B2 through some ...

  16. Search for high-energy muon neutrinos from the "naked-eye" GRB 080319B with the IceCube neutrino telescope

    DEFF Research Database (Denmark)

    Abbasi, R.; Abdou, Y.; Abu-Zayyad, T.

    2009-01-01

    We report on a search with the IceCube detector for high-energy muon neutrinos from GRB 080319B, one of the brightest gamma-ray bursts (GRBs) ever observed. The fireball model predicts that a mean of 0.1 events should be detected by IceCube for a bulk Lorentz boost of the jet of 300. In both the ......V and 2.2 PeV, which contains 90% of the expected events....

  17. H2 molecules and the intercloud medium

    International Nuclear Information System (INIS)

    Hill, J.K.; Hollenbach, D.J.

    1976-01-01

    We discuss expected column of densities of H 2 in the intercloud medium and the possible use of molecules as indicators of intercloud physical conditions. We treat molecule formation by the H - process and on graphite grains and show that the Barlow-Silk hypothesis of a 1 eV semichemical hydrogen-graphite bond leads to a large enhancement of the intercloud molecule formation rate. Rotational excitation calculations are presented for both cloud and intercloud conditions which show, in agreement with Jura, that the presently observed optically thin H 2 absorption components are more likely to originate in cold clouds than in the intercloud medium

  18. Identifying the Location in the Host Galaxy of Short GRB 1111l7A with the Chandra Sub- Arcsecond Position

    Science.gov (United States)

    Sakamoto, Takanori; Troja, E.; Aoki, K.; Guiriec, S.; Im, M.; Leloudas, G.; Malesani, D.; Melandri, A.; deUgartePostigo, A.; Urata, Y.; hide

    2012-01-01

    We present our successful program using Chandra for identifying the X-ray afterglow with sub-arcsecond accuracy for the short GRB 111117A d iscovered by Swift and Fermi. Thanks to our rapid target of opportuni ty request, Chandra clearly detected the X-ray afterglow, whereas no optical afterglow was found in deep optical observations. Instead, we clearly detect the host galaxy in optica; and also in near-infrared b ands. We found that the best photometric redshift fitofthe host is z = 1.31:(+0.46/-0.23) (90% confidence), making it one of the highest redshift short GRBs. Furthermore, we see an offset of 1.0+/-O.2 arcseco nds, which corresponds to 8.4+/-1.7 kpc aSBuming z= 1.31, between the host and the afterglow position. We discuss the importance of using Chandra for obtaining sub-arcsecond localization of the afterglow in X -rays for short GRBs to study GRB environments in great detail.

  19. Probing the Energetics of Dynactin Filament Assembly and the Binding of Cargo Adaptor Proteins Using Molecular Dynamics Simulation and Electrostatics-Based Structural Modeling.

    Science.gov (United States)

    Zheng, Wenjun

    2017-01-10

    Dynactin, a large multiprotein complex, binds with the cytoplasmic dynein-1 motor and various adaptor proteins to allow recruitment and transportation of cellular cargoes toward the minus end of microtubules. The structure of the dynactin complex is built around an actin-like minifilament with a defined length, which has been visualized in a high-resolution structure of the dynactin filament determined by cryo-electron microscopy (cryo-EM). To understand the energetic basis of dynactin filament assembly, we used molecular dynamics simulation to probe the intersubunit interactions among the actin-like proteins, various capping proteins, and four extended regions of the dynactin shoulder. Our simulations revealed stronger intersubunit interactions at the barbed and pointed ends of the filament and involving the extended regions (compared with the interactions within the filament), which may energetically drive filament termination by the capping proteins and recruitment of the actin-like proteins by the extended regions, two key features of the dynactin filament assembly process. Next, we modeled the unknown binding configuration among dynactin, dynein tails, and a number of coiled-coil adaptor proteins (including several Bicaudal-D and related proteins and three HOOK proteins), and predicted a key set of charged residues involved in their electrostatic interactions. Our modeling is consistent with previous findings of conserved regions, functional sites, and disease mutations in the adaptor proteins and will provide a structural framework for future functional and mutational studies of these adaptor proteins. In sum, this study yielded rich structural and energetic information about dynactin and associated adaptor proteins that cannot be directly obtained from the cryo-EM structures with limited resolutions.

  20. 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.

  1. 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.

  2. Deletion of the LIME adaptor protein minimally affects T and B cell development and function

    Czech Academy of Sciences Publication Activity Database

    Grégoire, C.; Šímová, Šárka; Wang, Y.; Sansoni, A.; Richelme, S.; Schmidr-Giese, A.; Simeoni, L.; Angelisová, Pavla; Reinhold, D.; Burkhart, S.; Hořejší, Václav; Malissen, B.; Malissen, M.

    2007-01-01

    Roč. 37, č. 11 (2007), s. 3259-3269 ISSN 0014-2980 R&D Projects: GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : LIME * adaptor protein * receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.662, year: 2007

  3. Molecules in strong laser fields. In depth study of H{sub 2} molecule

    Energy Technology Data Exchange (ETDEWEB)

    Awasthi, Manohar

    2009-10-29

    A method for solving the time-dependent Schroedinger equation (TDSE) describing the electronic motion of the molecules exposed to very short intense laser pulses has been developed. The time-dependent electronic wavefunction is expanded in terms of a superposition of field-free eigenstates. The field-free eigenstates are calculated in two ways. In the first approach, which is applicable to two electron systems like H{sub 2}, fully correlated field-free eigenstates are obtained in complete dimensionality using configuration-interaction calculation where the one-electron basis functions are built from B splines. In the second approach, which is even applicable to larger molecules, the field-free eigenstates are calculated within the single-active-electron (SAE) approximation using density functional theory. In general, the method can be divided into two parts, in the first part the field-free eigenstates are calculated and then in the second part a time propagation for the laser pulse parameters is performed. The H{sub 2} molecule is the testing ground for the implementation of both the methods. The reliability of the configuration interaction (CI) based method for the solution of TDSE (CI-TDSE) is tested by comparing results in the low-intensity regime to the prediction of lowest-order perturbation theory. Another test for the CI-TDSE method is in the united atom limit for the H{sub 2} molecule. By selecting a very small value of the internuclear distance close to zero for the H{sub 2} molecule, Helium atom is obtained. Once the functionality and the reliability of the method is established, it is used for obtaining accurate results for molecular hydrogen exposed to intense laser fields. The results for the standard 800 nm Titanium-Sapphire laser and its harmonics at 400 nm and 266 nm are shown. The results for a scan over a wide range of incident photon energies as well as dependence on the internuclear distance are presented. The photoelectron spectra including

  4. Crystal structure of Src-like adaptor protein 2 reveals close association of SH3 and SH2 domains through β-sheet formation.

    Science.gov (United States)

    Wybenga-Groot, Leanne E; McGlade, C Jane

    2013-12-01

    The Src-like adaptor proteins (SLAP/SLAP2) are key components of Cbl-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling in hematopoietic cells. SLAP and SLAP2 consist of adjacent SH3 and SH2 domains that are most similar in sequence to Src family kinases (SFKs). Notably, the SH3-SH2 connector sequence is significantly shorter in SLAP/SLAP2 than in SFKs. To understand the structural implication of a short SH3-SH2 connector sequence, we solved the crystal structure of a protein encompassing the SH3 domain, SH3-SH2 connector, and SH2 domain of SLAP2 (SLAP2-32). While both domains adopt typical folds, the short SH3-SH2 connector places them in close association. Strand βe of the SH3 domain interacts with strand βA of the SH2 domain, resulting in the formation of a continuous β sheet that spans the length of the protein. Disruption of the SH3/SH2 interface through mutagenesis decreases SLAP-32 stability in vitro, consistent with inter-domain binding being an important component of SLAP2 structure and function. The canonical peptide binding pockets of the SH3 and SH2 domains are fully accessible, in contrast to other protein structures that display direct interaction between SH3 and SH2 domains, in which either peptide binding surface is obstructed by the interaction. Our results reveal potential sites of novel interaction for SH3 and SH2 domains, and illustrate the adaptability of SH2 and SH3 domains in mediating interactions. As well, our results suggest that the SH3 and SH2 domains of SLAP2 function interdependently, with implications on their mode of substrate binding. © 2013.

  5. 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.

  6. Phospho-dependent binding of the clathrin AP2 adaptor complex to GABAA receptors regulates the efficacy of inhibitory synaptic transmission.

    Science.gov (United States)

    Kittler, Josef T; Chen, Guojun; Honing, Stephan; Bogdanov, Yury; McAinsh, Kristina; Arancibia-Carcamo, I Lorena; Jovanovic, Jasmina N; Pangalos, Menelas N; Haucke, Volker; Yan, Zhen; Moss, Stephen J

    2005-10-11

    The efficacy of synaptic inhibition depends on the number of gamma-aminobutyric acid type A receptors (GABA(A)Rs) expressed on the cell surface of neurons. The clathrin adaptor protein 2 (AP2) complex is a critical regulator of GABA(A)R endocytosis and, hence, surface receptor number. Here, we identify a previously uncharacterized atypical AP2 binding motif conserved within the intracellular domains of all GABA(A)R beta subunit isoforms. This AP2 binding motif (KTHLRRRSSQLK in the beta3 subunit) incorporates the major sites of serine phosphorylation within receptor beta subunits, and phosphorylation within this site inhibits AP2 binding. Furthermore, by using surface plasmon resonance, we establish that a peptide (pepbeta3) corresponding to the AP2 binding motif in the GABA(A)R beta3 subunit binds to AP2 with high affinity only when dephosphorylated. Moreover, the pepbeta3 peptide, but not its phosphorylated equivalent (pepbeta3-phos), enhanced the amplitude of miniature inhibitory synaptic current and whole cell GABA(A)R current. These effects of pepbeta3 on GABA(A)R current were occluded by inhibitors of dynamin-dependent endocytosis supporting an action of pepbeta3 on GABA(A)R endocytosis. Therefore phospho-dependent regulation of AP2 binding to GABA(A)Rs provides a mechanism to specify receptor cell surface number and the efficacy of inhibitory synaptic transmission.

  7. The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects.

    Science.gov (United States)

    Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A

    2016-09-19

    Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. The adaptor CRADD/RAIDD controls activation of endothelial cells by proinflammatory stimuli.

    Science.gov (United States)

    Qiao, Huan; Liu, Yan; Veach, Ruth A; Wylezinski, Lukasz; Hawiger, Jacek

    2014-08-08

    A hallmark of inflammation, increased vascular permeability, is induced in endothelial cells by multiple agonists through stimulus-coupled assembly of the CARMA3 signalosome, which contains the adaptor protein BCL10. Previously, we reported that BCL10 in immune cells is targeted by the "death" adaptor CRADD/RAIDD (CRADD), which negatively regulates nuclear factor κB (NFκB)-dependent cytokine and chemokine expression in T cells (Lin, Q., Liu, Y., Moore, D. J., Elizer, S. K., Veach, R. A., Hawiger, J., and Ruley, H. E. (2012) J. Immunol. 188, 2493-2497). This novel anti-inflammatory CRADD-BCL10 axis prompted us to analyze CRADD expression and its potential anti-inflammatory action in non-immune cells. We focused our study on microvascular endothelial cells because they play a key role in inflammation. We found that CRADD-deficient murine endothelial cells display heightened BCL10-mediated expression of the pleotropic proinflammatory cytokine IL-6 and chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) in response to LPS and thrombin. Moreover, these agonists also induce significantly increased permeability in cradd(-/-), as compared with cradd(+/+), primary murine endothelial cells. CRADD-deficient cells displayed more F-actin polymerization with concomitant disruption of adherens junctions. In turn, increasing intracellular CRADD by delivery of a novel recombinant cell-penetrating CRADD protein (CP-CRADD) restored endothelial barrier function and suppressed the induction of IL-6 and MCP-1 evoked by LPS and thrombin. Likewise, CP-CRADD enhanced barrier function in CRADD-sufficient endothelial cells. These results indicate that depletion of endogenous CRADD compromises endothelial barrier function in response to inflammatory signals. Thus, we define a novel function for CRADD in endothelial cells as an inducible suppressor of BCL10, a key mediator of responses to proinflammatory agonists. © 2014 by The American Society for Biochemistry and Molecular Biology

  9. GRB 090926A AND BRIGHT LATE-TIME FERMI LARGE AREA TELESCOPE GAMMA-RAY BURST AFTERGLOWS

    International Nuclear Information System (INIS)

    Swenson, C. A.; Roming, P. W. A.; Vetere, L.; Kennea, J. A.; Maxham, A.; Zhang, B. B.; Zhang, B.; Schady, P.; Holland, S. T.; Kuin, N. P. M.; Oates, S. R.; De Pasquale, M.; Page, K. L.

    2010-01-01

    GRB 090926A was detected by both the Gamma-ray Burst Monitor and Large Area Telescope (LAT) instruments on board the Fermi Gamma-ray Space Telescope. Swift follow-up observations began ∼13 hr after the initial trigger. The optical afterglow was detected for nearly 23 days post trigger, placing it in the long-lived category. The afterglow is of particular interest due to its brightness at late times, as well as the presence of optical flares at T0+10 5 s and later, which may indicate late-time central engine activity. The LAT has detected a total of 16 gamma-ray bursts; nine of these bursts, including GRB 090926A, also have been observed by Swift. Of the nine Swift-observed LAT bursts, six were detected by UVOT, with five of the bursts having bright, long-lived optical afterglows. In comparison, Swift has been operating for five years and has detected nearly 500 bursts, but has only seen ∼30% of bursts with optical afterglows that live longer than 10 5 s. We have calculated the predicted gamma-ray fluence, as would have been seen by the Burst Alert Telescope (BAT) on board Swift, of the LAT bursts to determine whether this high percentage of long-lived optical afterglows is unique, when compared to BAT-triggered bursts. We find that, with the exception of the short burst GRB 090510A, the predicted BAT fluences indicate that the LAT bursts are more energetic than 88% of all Swift bursts and also have brighter than average X-ray and optical afterglows.

  10. 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.

  11. Identification and Characterization of KCASH2 and KCASH3, 2 Novel Cullin3 Adaptors Suppressing Histone Deacetylase and Hedgehog Activity in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Enrico De Smaele

    2011-04-01

    Full Text Available Medulloblastoma is the most common pediatric malignant brain tumor, arising from aberrant cerebellar precursors' development, a process mainly controlled by Hedgehog (Hh signaling pathway. Histone deacetylase HDAC1 has been recently shown to modulate Hh signaling, deacetylating its effectors Gli1/2 and enhancing their transcriptional activity. Therefore, HDAC may represent a potential therapeutic target for Hh-dependent tumors, but still little information is available on the physiological mechanisms of HDAC regulation. The putative tumor suppressor RENKCTD11 acts through ubiquitination-dependent degradation of HDAC1, thereby affecting Hh activity and medulloblastoma growth. We identify and characterize here two RENKCTD11 homologues, defining a new family of proteins named KCASH, as “KCTD containing, Cullin3 adaptor, suppressor of Hedgehog.” Indeed, the novel genes (KCASH2KCTD21 and KCASH3KCTD6 share with RENKCTD11 a number of features, such as a BTB domain required for the formation of a Cullin3 ubiquitin ligase complex and HDAC1 ubiquitination and degradation capability, suppressing the acetylation-dependent Hh/Gli signaling. Expression of KCASH2 and -3 is observed in cerebellum, whereas epigenetic silencing and allelic deletion are observed in human medulloblastoma. Rescuing KCASHs expression reduces the Hedgehog-dependent medulloblastoma growth, suggesting that loss of members of this novel family of native HDAC inhibitors is crucial in sustaining Hh pathway-mediated tumorigenesis. Accordingly, they might represent a promising class of endogenous “agents” through which this pathway may be targeted.

  12. 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.

  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. 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.

  16. Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice.

    Science.gov (United States)

    Cero, Fadila Telarevic; Hillestad, Vigdis; Sjaastad, Ivar; Yndestad, Arne; Aukrust, Pål; Ranheim, Trine; Lunde, Ida Gjervold; Olsen, Maria Belland; Lien, Egil; Zhang, Lili; Haugstad, Solveig Bjærum; Løberg, Else Marit; Christensen, Geir; Larsen, Karl-Otto; Skjønsberg, Ole Henning

    2015-08-15

    Pulmonary hypertension is a serious condition that can lead to premature death. The mechanisms involved are incompletely understood although a role for the immune system has been suggested. Inflammasomes are part of the innate immune system and consist of the effector caspase-1 and a receptor, where nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) is the best characterized and interacts with the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC). To investigate whether ASC and NLRP3 inflammasome components are involved in hypoxia-induced pulmonary hypertension, we utilized mice deficient in ASC and NLRP3. Active caspase-1, IL-18, and IL-1β, which are regulated by inflammasomes, were measured in lung homogenates in wild-type (WT), ASC(-/-), and NLRP3(-/-) mice, and phenotypical changes related to pulmonary hypertension and right ventricular remodeling were characterized after hypoxic exposure. Right ventricular systolic pressure (RVSP) of ASC(-/-) mice was significantly lower than in WT exposed to hypoxia (40.8 ± 1.5 mmHg vs. 55.8 ± 2.4 mmHg, P right ventricular remodeling. RVSP of NLRP3(-/-) mice exposed to hypoxia was not significantly altered compared with WT hypoxia. Whereas hypoxia increased protein levels of caspase-1, IL-18, and IL-1β in WT and NLRP3(-/-) mice, this response was absent in ASC(-/-) mice. Moreover, ASC(-/-) mice displayed reduced muscularization and collagen deposition around arteries. In conclusion, hypoxia-induced elevated right ventricular pressure and remodeling were attenuated in mice lacking the inflammasome adaptor protein ASC, suggesting that inflammasomes play an important role in the pathogenesis of pulmonary hypertension. Copyright © 2015 the American Physiological Society.

  17. The Hypoxic Regulator of Sterol Synthesis Nro1 Is a Nuclear Import Adaptor

    Energy Technology Data Exchange (ETDEWEB)

    T Yeh; C Lee; L Amzel; P Espenshade; M Bianchet

    2011-12-31

    Fission yeast protein Sre1, the homolog of the mammalian sterol regulatory element-binding protein (SREBP), is a hypoxic transcription factor required for sterol homeostasis and low-oxygen growth. Nro1 regulates the stability of the N-terminal transcription factor domain of Sre1 (Sre1N) by inhibiting the action of the prolyl 4-hydroxylase-like Ofd1 in an oxygen-dependent manner. The crystal structure of Nro1 determined at 2.2 {angstrom} resolution shows an all-{alpha}-helical fold that can be divided into two domains: a small N-terminal domain, and a larger C-terminal HEAT-repeat domain. Follow-up studies showed that Nro1 defines a new class of nuclear import adaptor that functions both in Ofd1 nuclear localization and in the oxygen-dependent inhibition of Ofd1 to control the hypoxic response.

  18. Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

    Science.gov (United States)

    Matsuda, Shinji; Kakegawa, Wataru; Budisantoso, Timotheus; Nomura, Toshihiro; Kohda, Kazuhisa; Yuzaki, Michisuke

    2013-11-01

    Long-term depression (LTD) underlies learning and memory in various brain regions. Although postsynaptic AMPA receptor trafficking mediates LTD, its underlying molecular mechanisms remain largely unclear. Here we show that stargazin, a transmembrane AMPA receptor regulatory protein, forms a ternary complex with adaptor proteins AP-2 and AP-3A in hippocampal neurons, depending on its phosphorylation state. Inhibiting the stargazin-AP-2 interaction disrupts NMDA-induced AMPA receptor endocytosis, and inhibiting that of stargazin-AP-3A abrogates the late endosomal/lysosomal trafficking of AMPA receptors, thereby upregulating receptor recycling to the cell surface. Similarly, stargazin’s interaction with AP-2 or AP-3A is necessary for low-frequency stimulus-evoked LTD in CA1 hippocampal neurons. Thus, stargazin has a crucial role in NMDA-dependent LTD by regulating two trafficking pathways of AMPA receptors—transport from the cell surface to early endosomes and from early endosomes to late endosomes/lysosomes—through its sequential binding to AP-2 and AP-3A.

  19. 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

  20. GRB 130606A AS A PROBE OF THE INTERGALACTIC MEDIUM AND THE INTERSTELLAR MEDIUM IN A STAR-FORMING GALAXY IN THE FIRST Gyr AFTER THE BIG BANG

    International Nuclear Information System (INIS)

    Chornock, Ryan; Berger, Edo; Lunnan, Ragnhild; Drout, Maria R.; Fong Wenfai; Laskar, Tanmoy; Fox, Derek B.; Roth, Katherine C.

    2013-01-01

    We present high signal-to-noise ratio Gemini and MMT spectroscopy of the optical afterglow of the gamma-ray burst (GRB) 130606A at redshift z = 5.913, discovered by Swift. This is the first high-redshift GRB afterglow to have spectra of comparable quality to those of z ≈ 6 quasars. The data exhibit a smooth continuum at near-infrared wavelengths that is sharply cut off blueward of 8410 Å due to absorption from Lyα at redshift z ≈ 5.91, with some flux transmitted through the Lyα forest between 7000 and 7800 Å. We use column densities inferred from metal absorption lines to constrain the metallicity of the host galaxy between a lower limit of [Si/H] ∼> –1.7 and an upper limit of [S/H] ∼ GP eff (Lyα) > 6.4). This is comparable to the lowest-redshift Gunn-Peterson troughs found in quasar spectra. Some Lyβ and Lyγ transmission is detected in this redshift window, indicating that it is not completely opaque, and hence that the intergalactic medium (IGM) is nonetheless mostly ionized at these redshifts. We set a 2σ upper limit of 0.11 on the neutral fraction of the IGM at the redshift of the GRB from the lack of a Lyα red damping wing, assuming a model with a constant neutral density. GRB 130606A thus for the first time realizes the promise of GRBs as probes of the first galaxies and cosmic reionization

  1. New function of the adaptor protein SH2B1 in brain-derived neurotrophic factor-induced neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Chien-Hung Shih

    Full Text Available Neurite outgrowth is an essential process for the establishment of the nervous system. Brain-derived neurotrophic factor (BDNF binds to its receptor TrkB and regulates axonal and dendritic morphology of neurons through signal transduction and gene expression. SH2B1 is a signaling adaptor protein that regulates cellular signaling in various physiological processes. The purpose of this study is to investigate the role of SH2B1 in the development of the central nervous system. In this study, we show that knocking down SH2B1 reduces neurite formation of cortical neurons whereas overexpression of SH2B1β promotes the development of hippocampal neurons. We further demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth and signaling using the established PC12 cells stably expressing TrkB, SH2B1β or SH2B1β mutants. Our data indicate that overexpressing SH2B1β enhances BDNF-induced MEK-ERK1/2, and PI3K-AKT signaling pathways. Inhibition of MEK-ERK1/2 and PI3K-AKT pathways by specific inhibitors suggest that these two pathways are required for SH2B1β-promoted BDNF-induced neurite outgrowth. Moreover, SH2B1β enhances BDNF-stimulated phosphorylation of signal transducer and activator of transcription 3 at serine 727. Finally, our data indicate that the SH2 domain and tyrosine phosphorylation of SH2B1β contribute to BDNF-induced signaling pathways and neurite outgrowth. Taken together, these findings demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth through enhancing pathways involved MEK-ERK1/2 and PI3K-AKT.

  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. Downregulation of adaptor protein MyD88 compromises the angiogenic potential of B16 murine melanoma

    Science.gov (United States)

    Araya, Paula; Nuñez, Nicolás Gonzalo; Mena, Hebe Agustina; Bocco, José Luis; Negrotto, Soledad; Maccioni, Mariana

    2017-01-01

    The mechanisms that link inflammatory responses to cancer development remain a subject of intense investigation, emphasizing the need to better understand the cellular and molecular pathways that create a tumor promoting microenvironment. The myeloid differentiation primary response protein MyD88 acts as a main adaptor molecule for the signaling cascades initiated from Toll-like receptors (TLRs) and the interleukin 1 receptor (IL-1R). MyD88 has been shown to contribute to tumorigenesis in many inflammation-associated cancer models. In this study, we sought to better define the role of MyD88 in neoplastic cells using a murine melanoma model. Herein, we have demonstrated that MyD88 expression is required to maintain the angiogenic switch that supports B16 melanoma growth. By knocking down MyD88 we reduced TLR-mediated NF-κB activation with no evident effects over cell proliferation and survival. In addition, MyD88 downregulation was associated with a decrease of HIF1α levels and its target gene VEGF, in correlation with an impaired capability to induce capillary sprouting and tube formation of endothelial cells. Melanomas developed from cells lacking MyD88 showed an enhanced secretion of chemoattractant ligands such as CCL2, CXCL10 and CXCL1 and have an improved infiltration of macrophages to the tumor site. Our results imply that cell-autonomous signaling through MyD88 is required to sustain tumor growth and underscore its function as an important positive modulator of tumor angiogenesis. PMID:28662055

  4. 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).

  5. 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.

  6. Pitch adaptors of the ATLAS-SCT Endcap detector modules

    International Nuclear Information System (INIS)

    Ullan, M; Lozano, M; Campabadal, F; Fleta, C; Pellegrini, G; Garcia, C; Gonzalez, F

    2007-01-01

    Interconnection between detectors and electronics in modern High Energy Physics has become an issue of difficult solution due to the need to integrate both parts in the same module and the need for a low mass, simple connection. The Endcap section of the Semiconductor Tracker (SCT) of the ATLAS experiment at CERN has adopted the solution of using interface devices called pitch adaptors or fan-ins that, mounted on the modules, and using automatic wire bonding, connect the detector's multiple channels to the front-end electronics, adapting their different designs (pad pitch, dimensions, position). This paper describes the characteristics of these devices, the qualification tests that they have been submitted to, and the final results of their fabrication including quality assurance procedures

  7. FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset.

    Science.gov (United States)

    Yuan, Haiming; Huang, Linhuan; Hu, Xizi; Li, Qian; Sun, Xiaofang; Xie, Yingjun; Kong, Shu; Wang, Xiaoman

    2016-07-02

    Achondroplasia is a well-defined and common bone dysplasia. Genotype- and phenotype-level correlations have been found between the clinical symptoms of achondroplasia and achondroplasia-specific FGFR3 mutations. A 2-year-old boy with clinical features consistent with achondroplasia and Silver-Russell syndrome-like symptoms was found to carry a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene at c.1138G > A (p.Gly380Arg) and a de novo 574 kb duplication at chromosome 7p12.1 that involved the entire growth-factor receptor bound protein 10 (GRB10) gene. Using quantitative real-time PCR analysis, GRB10 was over-expressed, and, using enzyme-linked immunosorbent assays for IGF1 and IGF-binding protein-3 (IGFBP3), we found that IGF1 and IGFBP3 were low-expressed in this patient. We demonstrate that a combination of uncommon, rare and exceptional molecular defects related to the molecular bases of particular birth defects can be analyzed and diagnosed to potentially explain the observed variability in the combination of molecular defects.

  8. 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)

  9. 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.

  10. The TIR-domain containing adaptor TRAM is required for TLR7 mediated RANTES production.

    Directory of Open Access Journals (Sweden)

    Enda Shevlin

    Full Text Available Toll-like receptor 7 (TLR7 plays a vital role in the immune response to ssRNA viruses such as human rhinovirus (HRV and Influenza, against which there are currently no treatments or vaccines with long term efficacy available. Clearly, a more comprehensive understanding of the TLR7 signaling axis will contribute to its molecular targeting. TRIF related adaptor molecule (TRAM plays a vital role in TLR4 signaling by recruiting TRIF to TLR4, followed by endosomal trafficking of the complex and initiation of IRF3 dependent type I interferon production as well as NF-κB dependent pro-inflammatory cytokine production. Towards understanding the molecular mechanisms that regulate TLR7 functionality, we found that TRAM(-/- murine macrophages exhibited a transcriptional and translational impairment in TLR7 mediated RANTES, but not TNFα, production. Suppression of TRAM expression in human macrophages also resulted in an impairment in TLR7 mediated CCL5 and IFN-β, but not TNFα, gene induction. Furthermore, suppression of endogenous human TRAM expression in human macrophages significantly impaired RV16 induced CCL5 and IFNβ, but not TNFα gene induction. Additionally, TRAM-G2A dose-dependently inhibited TLR7 mediated activation of CCL5, IFNβ and IFNα reporter genes. TLR7-mediated phosphorylation and nuclear translocation of IRF3 was impaired in TRAM(-/- cells. Finally, co-immunoprecipitation studies indicated that TRAM physically interacts with MyD88 upon TLR7 stimulation, but not under basal conditions. Our results clearly demonstrate that TRAM plays a, hitherto unappreciated, role in TLR7 signaling through a novel signaling axis containing, but not limited to, MyD88, TRAM and IRF3 towards the activation of anti-viral immunity.

  11. A Small Molecule-Screening Pipeline to Evaluate the Therapeutic Potential of 2-Aminoimidazole Molecules Against Clostridium difficile

    Directory of Open Access Journals (Sweden)

    Rajani Thanissery

    2018-06-01

    Full Text Available Antibiotics are considered to be the first line of treatment for mild to moderately severe Clostridium difficile infection (CDI in humans. However, antibiotics are also risk factors for CDI as they decrease colonization resistance against C. difficile by altering the gut microbiota and metabolome. Finding compounds that selectively inhibit different stages of the C. difficile life cycle, while sparing the indigenous gut microbiota is important for the development of alternatives to standard antibiotic treatment. 2-aminoimidazole (2-AI molecules are known to disrupt bacterial protection mechanisms in antibiotic resistant bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus, but are yet to be evaluated against C. difficile. A comprehensive small molecule-screening pipeline was developed to investigate how novel small molecules affect different stages of the C. difficile life cycle (growth, toxin, and sporulation in vitro, and a library of commensal bacteria that are associated with colonization resistance against C. difficile. The initial screening tested the efficacy of eleven 2-AI molecules (compound 1 through 11 against C. difficile R20291 compared to a vancomycin (2 μg/ml control. Molecules were selected for their ability to inhibit C. difficile growth, toxin activity, and sporulation. Further testing included growth inhibition of other C. difficile strains (CD196, M68, CF5, 630, BI9, M120 belonging to distinct PCR ribotypes, and a commensal panel (Bacteroides fragilis, B. thetaiotaomicron, C. scindens, C. hylemonae, Lactobacillus acidophilus, L. gasseri, Escherichia coli, B. longum subsp. infantis. Three molecules compound 1 and 2, and 3 were microbicidal, whereas compounds 4, 7, 9, and 11 inhibited toxin activity without affecting the growth of C. difficile strains and the commensal microbiota. The antimicrobial and anti-toxin effects of 2-AI molecules need to be further characterized for mode of

  12. FERMI OBSERVATIONS OF GRB 090510: A SHORT-HARD GAMMA-RAY BURST WITH AN ADDITIONAL, HARD POWER-LAW COMPONENT FROM 10 keV TO GeV ENERGIES

    International Nuclear Information System (INIS)

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

    2010-01-01

    We present detailed observations of the bright short-hard gamma-ray burst GRB 090510 made with the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) on board the Fermi observatory. GRB 090510 is the first burst detected by the LAT that shows strong evidence for a deviation from a Band spectral fitting function during the prompt emission phase. The time-integrated spectrum is fit by the sum of a Band function with E peak = 3.9 ± 0.3 MeV, which is the highest yet measured, and a hard power-law component with photon index -1.62 ± 0.03 that dominates the emission below ∼20 keV and above ∼100 MeV. The onset of the high-energy spectral component appears to be delayed by ∼0.1 s with respect to the onset of a component well fit with a single Band function. A faint GBM pulse and a LAT photon are detected 0.5 s before the main pulse. During the prompt phase, the LAT detected a photon with energy 30.5 +5.8 -2.6 GeV, the highest ever measured from a short GRB. Observation of this photon sets a minimum bulk outflow Lorentz factor, Γ∼> 1200, using simple γγ opacity arguments for this GRB at redshift z = 0.903 and a variability timescale on the order of tens of ms for the ∼100 keV-few MeV flux. Stricter high confidence estimates imply Γ ∼> 1000 and still require that the outflows powering short GRBs are at least as highly relativistic as those of long-duration GRBs. Implications of the temporal behavior and power-law shape of the additional component on synchrotron/synchrotron self-Compton, external-shock synchrotron, and hadronic models are considered.

  13. Decreased SAP expression in T cells from patients with SLE contributes to early signaling abnormalities and reduced IL-2 production

    Science.gov (United States)

    Karampetsou, Maria P.; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C.; Tsokos, George C.

    2016-01-01

    T cells from patients with systemic lupus erythematosus (SLE) display a number of functions including increased early signaling events following engagement of the T cell receptor (TCR). Signaling lymphocytic activation molecule family (SLAMF) cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating immune response. Here we present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and 3 men with SLE independently of disease activity. In SLE T cells the SAP protein is also subject to increased degradation by a caspase-3. Forced expression of SAP in SLE T cells simultaneously heightened IL-2 production, calcium (Ca2+) responses and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR antibodies, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

  14. ALMA Observations of the Host Galaxy of GRB 090423 at z = 8.23: Deep Limits on Obscured Star Formation 630 Million Years after the Big Bang

    Science.gov (United States)

    Berger, E.; Zauderer, B. A.; Chary, R.-R.; Laskar, T.; Chornock, R.; Tanvir, N. R.; Stanway, E. R.; Levan, A. J.; Levesque, E. M.; Davies, J. E.

    2014-12-01

    We present rest-frame far-infrared (FIR) and optical observations of the host galaxy of GRB 090423 at z = 8.23 from the Atacama Large Millimeter Array (ALMA) and the Spitzer Space Telescope, respectively. The host remains undetected to 3σ limits of F ν(222 GHz) Space Telescope rest-frame ultraviolet (UV) observations is SFRUV ~ 4 (Lyman break galaxies, Lyα emitters, and submillimeter galaxies) and find that our limit on the FIR luminosity is the most constraining to date, although the field galaxies have much larger rest-frame UV/optical luminosities than the host of GRB 090423 by virtue of their selection techniques. We conclude that GRB host galaxies at z >~ 4, especially those with measured interstellar medium metallicities from afterglow spectroscopy, are an attractive sample for future ALMA studies of high redshift obscured star formation.

  15. Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.

    Science.gov (United States)

    Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C; Tsokos, George C

    2016-06-15

    T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. Copyright © 2016 by The American Association of Immunologists, Inc.

  16. Mixed Quantum/Classical Theory for Molecule-Molecule Inelastic Scattering: Derivations of Equations and Application to N2 + H2 System.

    Science.gov (United States)

    Semenov, Alexander; Babikov, Dmitri

    2015-12-17

    The mixed quantum classical theory, MQCT, for inelastic scattering of two molecules is developed, in which the internal (rotational, vibrational) motion of both collision partners is treated with quantum mechanics, and the molecule-molecule scattering (translational motion) is described by classical trajectories. The resultant MQCT formalism includes a system of coupled differential equations for quantum probability amplitudes, and the classical equations of motion in the mean-field potential. Numerical tests of this theory are carried out for several most important rotational state-to-state transitions in the N2 + H2 system, in a broad range of collision energies. Besides scattering resonances (at low collision energies) excellent agreement with full-quantum results is obtained, including the excitation thresholds, the maxima of cross sections, and even some smaller features, such as slight oscillations of energy dependencies. Most importantly, at higher energies the results of MQCT are nearly identical to the full quantum results, which makes this approach a good alternative to the full-quantum calculations that become computationally expensive at higher collision energies and for heavier collision partners. Extensions of this theory to include vibrational transitions or general asymmetric-top rotor (polyatomic) molecules are relatively straightforward.

  17. Constraints on Born-Infeld gravity from the speed of gravitational waves after GW170817 and GRB 170817A

    Science.gov (United States)

    Jana, Soumya; Chakravarty, Girish Kumar; Mohanty, Subhendra

    2018-04-01

    The observations of gravitational waves from the binary neutron star merger event GW170817 and the subsequent observation of its electromagnetic counterparts from the gamma-ray burst GRB 170817A provide us a significant opportunity to study theories of gravity beyond general relativity. An important outcome of these observations is that they constrain the difference between the speed of gravity and the speed of light to less than 10-15c . Also, the time delay between the arrivals of gravitational waves at different detectors constrains the speed of gravity at the Earth to be in the range 0.55 c 2 . Similarly, from the time delay between the signals of GW170817 and GRB 170817A, in a background Friedmann-Robertson-Walker universe, we obtain |κ |≲1037 m2 . Although the bounds on κ are weak compared to other earlier bounds from the study of neutron stars, stellar evolution, primordial nucleosynthesis, etc., our bounds are from direct observations and thus worth noting.

  18. 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

  19. Stabilizing photoassociated Cs2 molecules by optimal control

    International Nuclear Information System (INIS)

    Zhang Wei; Xie Ting; Huang Yin; Wang Gao-Ren; Cong Shu-Lin

    2013-01-01

    We demonstrate theoretically that photoassociated molecules can be stabilized to deeply bound states. This process is achieved by transferring the population from the outer well to the inner well using the optimal control theory, the Cs 2 molecule is taken as an example. Numerical calculations show that weakly bound molecules formed in the outer well by a pump pulse can be compressed to the inner well via a vibrational level of the ground electronic state as an intermediary by an additionally optimized laser pulse. The positively chirped pulse can enhance the population of the target state. With a transform-limited dump pulse, nearly all the photoassociated molecules in the inner well of the excited electronic state can be transferred to the deeply vibrational level of the ground electronic state. (atomic and molecular physics)

  20. Stabilizing photoassociated Cs2 molecules by optimal control

    Science.gov (United States)

    Zhang, Wei; Xie, Ting; Huang, Yin; Wang, Gao-Ren; Cong, Shu-Lin

    2013-01-01

    We demonstrate theoretically that photoassociated molecules can be stabilized to deeply bound states. This process is achieved by transferring the population from the outer well to the inner well using the optimal control theory, the Cs2 molecule is taken as an example. Numerical calculations show that weakly bound molecules formed in the outer well by a pump pulse can be compressed to the inner well via a vibrational level of the ground electronic state as an intermediary by an additionally optimized laser pulse. The positively chirped pulse can enhance the population of the target state. With a transform-limited dump pulse, nearly all the photoassociated molecules in the inner well of the excited electronic state can be transferred to the deeply vibrational level of the ground electronic state.

  1. GRB 120521C at z ∼ 6 and the properties of high-redshift γ-ray bursts

    Energy Technology Data Exchange (ETDEWEB)

    Laskar, Tanmoy; Berger, Edo; Zauderer, B. Ashley; Margutti, Raffaella; Fong, Wen-fai [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Tanvir, Nial; Wiersema, Klaas [Department of Physics and Astronomy, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Levan, Andrew [Department of Physics, University of Warwick, Coventry CV4 7AL (United Kingdom); Perley, Daniel [Department of Astronomy, California Institute of Technology, MC 249-17, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Menten, Karl [Max-Planck-Institut für Radioastronomie, Auf dem Hügel 69, D-53121 Bonn (Germany); Hrudkova, Marie [Isaac Newton Group of Telescopes, Apartado de Correos 321, E-387 00 Santa Cruz de la Palma, Canary Islands (Spain)

    2014-01-20

    We present optical, near-infrared, and radio observations of the afterglow of GRB 120521C. By modeling the multi-wavelength data set, we derive a photometric redshift of z ≈ 6.0, which we confirm with a low signal-to-noise ratio spectrum of the afterglow. We find that a model with a constant-density environment provides a good fit to the afterglow data, with an inferred density of n ≲ 0.05 cm{sup –3}. The radio observations reveal the presence of a jet break at t {sub jet} ≈ 7 d, corresponding to a jet opening angle of θ{sub jet} ≈ 3°. The beaming-corrected γ-ray and kinetic energies are E {sub γ} ≈ E{sub K} ≈ 3 × 10{sup 50} erg. We quantify the uncertainties in our results using a detailed Markov Chain Monte Carlo analysis, which allows us to uncover degeneracies between the physical parameters of the explosion. To compare GRB 120521C to other high-redshift bursts in a uniform manner we re-fit all available afterglow data for the two other bursts at z ≳ 6 with radio detections (GRBs 050904 and 090423). We find a jet break at t {sub jet} ≈ 15 d for GRB 090423, in contrast to previous work. Based on these three events, we find that γ-ray bursts (GRBs) at z ≳ 6 appear to explode in constant-density environments, and exhibit a wide range of energies and densities that span the range inferred for lower redshift bursts. On the other hand, we find a hint for narrower jets in the z ≳ 6 bursts, potentially indicating a larger true event rate at these redshifts. Overall, our results indicate that long GRBs share a common progenitor population at least to z ∼ 8.

  2. What can BeppoSAX tell us about short GRBs: An update from the subsecond GRB project

    International Nuclear Information System (INIS)

    Gandolfi, G.; Costa, E.; Feroci, M.; Piro, L.; Smith, M.J.S.; Muller, J.M.; Coletta, A.; Celidonio, G.; Di Ciolo, L.; Paolino, A.; Tarei, G.; Tassone, G.; Frontera, F.

    2000-01-01

    We present some statistical considerations on the BeppoSAX hunt for subsecond GRBs at the Scientific Operation Center. Archival analysis of a BATSE/SAX sub-sample of bursts indicates that the GRB Monitor is sensitive to short (≤2 sec) events, that are in fact ≅22% of the total. The non-detection of corresponding prompt X-ray counterparts to short bursts in the Wide Field Cameras, in about 3 years of operations, is discussed: with present data no implications on the X-to-γ-ray spectra of short vs. long GRBs may be inferred. Finally, the status of searching procedures at the SOC is reviewed

  3. 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.

  4. Identification of Atg2 and ArfGAP1 as Candidate Genetic Modifiers of the Eye Pigmentation Phenotype of Adaptor Protein-3 (AP-3) Mutants in Drosophila melanogaster.

    Science.gov (United States)

    Rodriguez-Fernandez, Imilce A; Dell'Angelica, Esteban C

    2015-01-01

    The Adaptor Protein (AP)-3 complex is an evolutionary conserved, molecular sorting device that mediates the intracellular trafficking of proteins to lysosomes and related organelles. Genetic defects in AP-3 subunits lead to impaired biogenesis of lysosome-related organelles (LROs) such as mammalian melanosomes and insect eye pigment granules. In this work, we have performed a forward screening for genetic modifiers of AP-3 function in the fruit fly, Drosophila melanogaster. Specifically, we have tested collections of large multi-gene deletions--which together covered most of the autosomal chromosomes-to identify chromosomal regions that, when deleted in single copy, enhanced or ameliorated the eye pigmentation phenotype of two independent AP-3 subunit mutants. Fine-mapping led us to define two non-overlapping, relatively small critical regions within fly chromosome 3. The first critical region included the Atg2 gene, which encodes a conserved protein involved in autophagy. Loss of one functional copy of Atg2 ameliorated the pigmentation defects of mutants in AP-3 subunits as well as in two other genes previously implicated in LRO biogenesis, namely Blos1 and lightoid, and even increased the eye pigment content of wild-type flies. The second critical region included the ArfGAP1 gene, which encodes a conserved GTPase-activating protein with specificity towards GTPases of the Arf family. Loss of a single functional copy of the ArfGAP1 gene ameliorated the pigmentation phenotype of AP-3 mutants but did not to modify the eye pigmentation of wild-type flies or mutants in Blos1 or lightoid. Strikingly, loss of the second functional copy of the gene did not modify the phenotype of AP-3 mutants any further but elicited early lethality in males and abnormal eye morphology when combined with mutations in Blos1 and lightoid, respectively. These results provide genetic evidence for new functional links connecting the machinery for biogenesis of LROs with molecules implicated in

  5. Identification of Atg2 and ArfGAP1 as Candidate Genetic Modifiers of the Eye Pigmentation Phenotype of Adaptor Protein-3 (AP-3 Mutants in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Imilce A Rodriguez-Fernandez

    Full Text Available The Adaptor Protein (AP-3 complex is an evolutionary conserved, molecular sorting device that mediates the intracellular trafficking of proteins to lysosomes and related organelles. Genetic defects in AP-3 subunits lead to impaired biogenesis of lysosome-related organelles (LROs such as mammalian melanosomes and insect eye pigment granules. In this work, we have performed a forward screening for genetic modifiers of AP-3 function in the fruit fly, Drosophila melanogaster. Specifically, we have tested collections of large multi-gene deletions--which together covered most of the autosomal chromosomes-to identify chromosomal regions that, when deleted in single copy, enhanced or ameliorated the eye pigmentation phenotype of two independent AP-3 subunit mutants. Fine-mapping led us to define two non-overlapping, relatively small critical regions within fly chromosome 3. The first critical region included the Atg2 gene, which encodes a conserved protein involved in autophagy. Loss of one functional copy of Atg2 ameliorated the pigmentation defects of mutants in AP-3 subunits as well as in two other genes previously implicated in LRO biogenesis, namely Blos1 and lightoid, and even increased the eye pigment content of wild-type flies. The second critical region included the ArfGAP1 gene, which encodes a conserved GTPase-activating protein with specificity towards GTPases of the Arf family. Loss of a single functional copy of the ArfGAP1 gene ameliorated the pigmentation phenotype of AP-3 mutants but did not to modify the eye pigmentation of wild-type flies or mutants in Blos1 or lightoid. Strikingly, loss of the second functional copy of the gene did not modify the phenotype of AP-3 mutants any further but elicited early lethality in males and abnormal eye morphology when combined with mutations in Blos1 and lightoid, respectively. These results provide genetic evidence for new functional links connecting the machinery for biogenesis of LROs with

  6. 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.

  7. Increased Level of Phosphorylated ShcA Measured by Chemiluminescence-Linked Immunoassay Is a Predictor of Good Prognosis in Primary Breast Cancer Expressing Low Levels of Estrogen Receptor

    International Nuclear Information System (INIS)

    Cicenas, Jonas; Küng, Willy; Eppenberger, Urs; Eppenberger-Castori, Serenella

    2010-01-01

    The SH2 domain-containing adaptor protein ShcA is a proto-oncogene involved in growth factor receptor signaling. The role of phosphorylated ShcA is to link receptor tyrosine kinases with the SH2-containing adaptor protein Grb2, thus facilitating signal transduction from receptor tyrosine kinases to Ras, leading to MAPK activation. The present study was designed to investigate the prognostic significance of phosphorylated ShcA in primary breast cancer and its association in the interactions between the ER and ErbB2 pathways. Using a two-site chemiluminescence-linked immunosorbent assay, we detected the quantitative expression levels of total tyrosine- and threonine-phosphorylated ShcA in cytosol fractions obtained from fresh frozen tissue samples of 153 selected primary breast cancer patients. ShcA phosphorylation was not associated with nodal status, estrogen receptor (ER) status or grading. High levels of both tyrosine (pYShcA) and serine (pSShcA) phosphorylated ShcA correlated with good prognosis (p < 0.01), with respect to both disease-free (DFS) and overall survival (OS). In addition, pShcA levels were found to correlate with threonine-phosphorylated ErbB2 and inversely with phosphorylated Akt (pAkt), as well as ErbB2 and ER expression levels. Our findings demonstrate that ShcA activation in primary breast cancer patients correlates with low levels of ER, and is associated with good prognosis

  8. Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders

    OpenAIRE

    Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H. Phillip

    2007-01-01

    Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk i...

  9. GRB 130606A AS A PROBE OF THE INTERGALACTIC MEDIUM AND THE INTERSTELLAR MEDIUM IN A STAR-FORMING GALAXY IN THE FIRST Gyr AFTER THE BIG BANG

    Energy Technology Data Exchange (ETDEWEB)

    Chornock, Ryan; Berger, Edo; Lunnan, Ragnhild; Drout, Maria R.; Fong Wenfai; Laskar, Tanmoy [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Fox, Derek B. [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Roth, Katherine C., E-mail: rchornock@cfa.harvard.edu [Gemini Observatory, 670 North Aohoku Place, Hilo, HI 96720 (United States)

    2013-09-01

    We present high signal-to-noise ratio Gemini and MMT spectroscopy of the optical afterglow of the gamma-ray burst (GRB) 130606A at redshift z = 5.913, discovered by Swift. This is the first high-redshift GRB afterglow to have spectra of comparable quality to those of z Almost-Equal-To 6 quasars. The data exhibit a smooth continuum at near-infrared wavelengths that is sharply cut off blueward of 8410 A due to absorption from Ly{alpha} at redshift z Almost-Equal-To 5.91, with some flux transmitted through the Ly{alpha} forest between 7000 and 7800 A. We use column densities inferred from metal absorption lines to constrain the metallicity of the host galaxy between a lower limit of [Si/H] {approx}> -1.7 and an upper limit of [S/H] {approx}< -0.5 set by the non-detection of S II absorption. We demonstrate consistency between the dramatic evolution in the transmission fraction of Ly{alpha} seen in this spectrum over the redshift range z = 4.9-5.85 with that previously measured from observations of high-redshift quasars. There is an extended redshift interval of {Delta}z = 0.12 in the Ly{alpha} forest at z = 5.77 with no detected transmission, leading to a 3{sigma} upper limit on the mean Ly{alpha} transmission fraction of {approx}<0.2% (or {tau}{sub GP}{sup eff} (Ly{alpha}) > 6.4). This is comparable to the lowest-redshift Gunn-Peterson troughs found in quasar spectra. Some Ly{beta} and Ly{gamma} transmission is detected in this redshift window, indicating that it is not completely opaque, and hence that the intergalactic medium (IGM) is nonetheless mostly ionized at these redshifts. We set a 2{sigma} upper limit of 0.11 on the neutral fraction of the IGM at the redshift of the GRB from the lack of a Ly{alpha} red damping wing, assuming a model with a constant neutral density. GRB 130606A thus for the first time realizes the promise of GRBs as probes of the first galaxies and cosmic reionization.

  10. Closing in on a Short-Hard Burst Progenitor: Constraints From Early-Time Optical Imaging and Spectroscopy of a Possible Host Galaxy of GRB 050509b

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, Joshua S.; Prochaska, J.X.; Pooley, D.; Blake, C.W.; Foley, R.J.; Jha, S.; Ramirez-Ruiz, E.; Granot, J.; Filippenko, A.V.; Sigurdsson, S.; Barth, A.J.; Chen,; Cooper, M.C.; Falco, E.E.; Gal, R.R.; Gerke, B.F.; Gladders, M.D.; Greene, J.E.; Hennanwi, J.; Ho, L.C.; Hurley, K.; /UC, Berkeley, Astron. Dept. /Lick Observ.

    2005-06-07

    The localization of the short-duration, hard-spectrum gamma-ray burst GRB050509b by the Swift satellite was a watershed event. Never before had a member of this mysterious subclass of classic GRBs been rapidly and precisely positioned in a sky accessible to the bevy of ground-based follow-up facilities. Thanks to the nearly immediate relay of the GRB position by Swift, we began imaging the GRB field 8 minutes after the burst and have continued during the 8 days since. Though the Swift X-ray Telescope (XRT) discovered an X-ray afterglow of GRB050509b, the first ever of a short-hard burst, thus far no convincing optical/infrared candidate afterglow or supernova has been found for the object. We present a re-analysis of the XRT afterglow and find an absolute position of R.A. = 12h36m13.59s, Decl. = +28{sup o}59'04.9'' (J2000), with a 1{sigma} uncertainty of 3.68'' in R.A., 3.52'' in Decl.; this is about 4'' to the west of the XRT position reported previously. Close to this position is a bright elliptical galaxy with redshift z = 0.2248 {+-} 0.0002, about 1' from the center of a rich cluster of galaxies. This cluster has detectable diffuse emission, with a temperature of kT = 5.25{sub -1.68}{sup +3.36} keV. We also find several ({approx}11) much fainter galaxies consistent with the XRT position from deep Keck imaging and have obtained Gemini spectra of several of these sources. Nevertheless we argue, based on positional coincidences, that the GRB and the bright elliptical are likely to be physically related. We thus have discovered reasonable evidence that at least some short-duration, hard-spectra GRBs are at cosmological distances. We also explore the connection of the properties of the burst and the afterglow, finding that GRB050509b was underluminous in both of these relative to long-duration GRBs. However, we also demonstrate that the ratio of the blast-wave energy to the {gamma}-ray energy is consistent with that

  11. A JET BREAK IN THE X-RAY LIGHT CURVE OF SHORT GRB 111020A: IMPLICATIONS FOR ENERGETICS AND RATES

    International Nuclear Information System (INIS)

    Fong, W.; Berger, E.; Margutti, R.; Zauderer, B. A.; Czekala, I.; Chornock, R.; Troja, E.; Gehrels, N.; Sakamoto, T.; Fox, D. B.; Podsiadlowski, P.

    2012-01-01

    We present broadband observations of the afterglow and environment of the short GRB 111020A. An extensive X-ray light curve from Swift/XRT, XMM-Newton, and Chandra, spanning ∼100 s to 10 days after the burst, reveals a significant break at δt ≈ 2 days with pre- and post-break decline rates of α X,1 ≈ –0.78 and α X,2 ∼ j ≈ 3°-8°. The resulting beaming-corrected γ-ray (10-1000 keV band) and blast-wave kinetic energies are (2-3) × 10 48 erg and (0.3-2) × 10 49 erg, respectively, with the range depending on the unknown redshift of the burst. We report a radio afterglow limit of c X , constrains the circumburst density to n 0 ∼ 0.01-0.1 cm –3 . Optical observations provide an afterglow limit of i ∼> 24.4 mag at 18 hr after the burst and reveal a potential host galaxy with i ≈ 24.3 mag. The subarcsecond localization from Chandra provides a precise offset of 0.''80 ± 0.''11 (1σ) from this galaxy corresponding to an offset of 5-7 kpc for z 0.5-1.5. We find a high excess neutral hydrogen column density of (7.5 ± 2.0) × 10 21 cm –2 (z = 0). Our observations demonstrate that a growing fraction of short gamma-ray bursts (GRBs) are collimated, which may lead to a true event rate of ∼> 100-1000 Gpc –3 yr –1 , in good agreement with the NS-NS merger rate of ≈200-3000 Gpc –3 yr –1 . This consistency is promising for coincident short GRB-gravitational wave searches in the forthcoming era of Advanced LIGO/VIRGO.

  12. 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

  13. 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...

  14. Trapping and interactions of an ultracold gas of Cs2 molecules

    International Nuclear Information System (INIS)

    Mark, M.; Kraemer, T.; Herbig, J.; Waldburger, P.; Naegerl, H.C.; Chin, C.; Grimm, R.

    2005-01-01

    Full text: We investigate dynamics and interactions of Cs 2 dimers in a CO2-laser dipole trap. Starting with a Bose-Einstein condensate (BEC) of 2.2 x 10 5 Cs atoms, we create ultracold molecules in a single, weakly bound quantum state by sweeping the magnetic field across a narrow Feshbach resonance. When the molecules are created in free space, the conversion efficiency exceeds 30 %, yielding up to 50000 molecules. In our trapping experiments, about 6000 ultracold Cs 2 dimers are prepared in the optical trap at a temperature of 200 nK. We transfer the trapped molecules from the initial molecular state to other molecular states by following avoided crossings. We find two magnetically tunable resonances in collisions between the molecules for one of the molecular states. We interpret these Feshbach-liKEX resonances as being induced by Cs 4 bound states near the molecular scattering continuum. Further, we have discovered a new molecular state with very large orbital angular momentum of l = 8. This state is very weakly coupled to one of the initial molecular states. We use the associated avoided crossing as a molecular beam splitter to realize a molecular Ramsey-type interferometer. Refs. 2 (author)

  15. The Very Red Afterglow of GRB 000418: Further Evidence for Dust Extinction in a Gamma-Ray Burst Host Galaxy

    Science.gov (United States)

    Klose, S.; Stecklum, B.; Masetti, N.; Pian, E.; Palazzi, E.; Henden, A. A.; Hartmann, D. H.; Fischer, O.; Gorosabel, J.; Sánchez-Fernández, C.; Butler, D.; Ott, Th.; Hippler, S.; Kasper, M.; Weiss, R.; Castro-Tirado, A.; Greiner, J.; Bartolini, C.; Guarnieri, A.; Piccioni, A.; Benetti, S.; Ghinassi, F.; Magazzú, A.; Hurley, K.; Cline, T.; Trombka, J.; McClanahan, T.; Starr, R.; Goldsten, J.; Gold, R.; Mazets, E.; Golenetskii, S.; Noeske, K.; Papaderos, P.; Vreeswijk, P. M.; Tanvir, N.; Oscoz, A.; Muñoz, J. A.; Castro Cerón, J. M.

    2000-12-01

    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-infrared. During the first 10 days its R-band afterglow was well characterized by a single power-law decay with a slope of 0.86. However, at later times the temporal evolution of the afterglow flattens with respect to a simple power-law decay. Attributing this to an underlying host galaxy, we find its magnitude to be R=23.9 and an intrinsic afterglow decay slope of 1.22. The afterglow was very red with R-K~4 mag. The observations can be explained by an adiabatic, spherical fireball solution and a heavy reddening due to dust extinction in the host galaxy. This supports the picture that (long) bursts are associated with events in star-forming regions. Based on observations collected at the Bologna Astronomical Observatory in Loiano, Italy; at the TNG, Canary Islands, Spain; at the German-Spanish Astronomical Centre, Calar Alto, operated by the Max-Planck-Institut for Astronomy, Heidelberg, jointly with the Spanish National Commission for Astronomy; at the US Naval Observatory; and at the UK Infrared Telescope.

  16. 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.

  17. Decomposition of 2-((2-methoxyphenyl)diazenyl)benzene-1,3,5-triol molecule by an argon plasma jet

    Science.gov (United States)

    Tanışlı, Murat; Taşal, Erol

    2018-05-01

    In this study, we have presented the effects of the argon plasma on a 2-((2-methoxyphenyl)diazenyl)benzene-1,3,5-triol molecule—AZO compound (abbreviated as 2MDB)—under atmospheric pressure. In order to do this, the validated molecule has been considered and plasma has been used to modify it. The atmospheric pressure plasma jet system was specially designed for performing decomposing processes of the 2MDB molecule. The characterizations before and after the application of plasma—which takes only 3 minutes under atmospheric pressure conditions, to dissolve the 2MDB molecule in ethanol and methanol solutions—were examined using the Fourier transform infrared and Ultraviolet-Visible (UV-Vis) spectroscopies. After the plasma treatment, the molecule was broken at -C-N=N-C-C bond. Accurate and important changes are seen clearly from the results. In addition, according to UV-Vis spectra, π-π* electronic transitions related to -N=N- AZO bridge for the 2MDB molecule in polar-aprotic solvents such as ethanol and methanol were recorded as strong transitions. The new photoproducts such as -C-N-N=C and C=O were obtained from the 2MDB molecule.

  18. Detailed optical and near-infrared polarimetry, spectroscopy and broad-band photometry of the afterglow of GRB 091018: polarization evolution

    NARCIS (Netherlands)

    Wiersema, K.; Curran, P.; Krühler, T.; Melandri, A.; Rol, E.; Starling, R.L.C.; Tanvir, N.R.; van der Horst, A.J.; Covino, S.; Fynbo, J.P.U.; Goldoni, P.; Gorosabel, J.; Hjorth, J.; Klose, S.; Mundell, C.G.; O'Brien, P.T.; Palazzi, E.; Wijers, R.A.M.J.; D'Elia, V.; Evans, P.A.; Filgas, R.; Gomboc, A.; Greiner, J.; Guidorzi, C.; Kaper, L.; Kobayashi, S.; Kouveliotou, C.; Levan, A.J.; Rossi, A..; Rowlinson, A.; Steele, I.A.; de Ugarte Postigo, A.; Vergani, S.D.

    2012-01-01

    Follow-up observations of large numbers of gamma-ray burst (GRB) afterglows, facilitated by the Swift satellite, have produced a large sample of spectral energy distributions and light curves, from which their basic micro- and macro-physical parameters can in principle be derived. However, a number

  19. First-principles study on the structure and electronic property of gas molecules adsorption on Ge2Li2 monolayer

    Science.gov (United States)

    Hu, Yiwei; Long, Linbo; Mao, Yuliang; Zhong, Jianxin

    2018-06-01

    Using first-principles methods, we have studied the adsorption of gas molecules (CO2, CH4, H2S, H2 and NH3) on two dimensional Ge2Li2 monolayer. The adsorption geometries, adsorption energies, charge transfer, and band structures of above mentioned gas molecules adsorption on Ge2Li2 monolayer are analyzed. It is found that the adsorption of CO2 on Ge2Li2 monolayer is a kind of strong chemisorption, while other gas molecules such as CH4, H2S, H2 and NH3 are physisorption. The strong covalent binding is formed between the CO2 molecule and the nearest Ge atom in Ge2Li2 monolayer. This adsorption of CO2 molecule on Ge2Li2 monolayer leads to a direct energy gap of 0.304 eV. Other gas molecules exhibit mainly ionic binding to the nearest Li atoms in Ge2Li2 monolayer, which leads to indirect energy gap after adsorptions. Furthermore, it is found that the work function of Ge2Li2 monolayer is sensitive with the variation of adsorbents. Our results reveal that the Ge2Li2 monolayer can be used as a kind of nano device for gas molecules sensor.

  20. Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains.

    Science.gov (United States)

    Sha, Fern; Gencer, Emel Basak; Georgeon, Sandrine; Koide, Akiko; Yasui, Norihisa; Koide, Shohei; Hantschel, Oliver

    2013-09-10

    The dysregulated tyrosine kinase BCR-ABL causes chronic myelogenous leukemia in humans and forms a large multiprotein complex that includes the Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2). The expression of SHP2 is necessary for BCR-ABL-dependent oncogenic transformation, but the precise signaling mechanisms of SHP2 are not well understood. We have developed binding proteins, termed monobodies, for the N- and C-terminal SH2 domains of SHP2. Intracellular expression followed by interactome analysis showed that the monobodies are essentially monospecific to SHP2. Two crystal structures revealed that the monobodies occupy the phosphopeptide-binding sites of the SH2 domains and thus can serve as competitors of SH2-phosphotyrosine interactions. Surprisingly, the segments of both monobodies that bind to the peptide-binding grooves run in the opposite direction to that of canonical phosphotyrosine peptides, which may contribute to their exquisite specificity. When expressed in cells, monobodies targeting the N-SH2 domain disrupted the interaction of SHP2 with its upstream activator, the Grb2-associated binder 2 adaptor protein, suggesting decoupling of SHP2 from the BCR-ABL protein complex. Inhibition of either N-SH2 or C-SH2 was sufficient to inhibit two tyrosine phosphorylation events that are critical for SHP2 catalytic activity and to block ERK activation. In contrast, targeting the N-SH2 or C-SH2 revealed distinct roles of the two SH2 domains in downstream signaling, such as the phosphorylation of paxillin and signal transducer and activator of transcription 5. Our results delineate a hierarchy of function for the SH2 domains of SHP2 and validate monobodies as potent and specific antagonists of protein-protein interactions in cancer cells.

  1. Efficient production of long-lived ultracold Sr2 molecules

    Science.gov (United States)

    Ciamei, Alessio; Bayerle, Alex; Chen, Chun-Chia; Pasquiou, Benjamin; Schreck, Florian

    2017-07-01

    We associate Sr atom pairs on sites of a Mott insulator optically and coherently into weakly bound ground-state molecules, achieving an efficiency above 80%. This efficiency is 2.5 times higher than in our previous work [S. Stellmer, B. Pasquiou, R. Grimm, and F. Schreck, Phys. Rev. Lett. 109, 115302 (2012), 10.1103/PhysRevLett.109.115302] and obtained through two improvements. First, the lifetime of the molecules is increased beyond one minute by using an optical lattice wavelength that is further detuned from molecular transitions. Second, we compensate undesired dynamic light shifts that occur during the stimulated Raman adiabatic passage (STIRAP) used for molecule association. We also characterize and model STIRAP, providing insights into its limitations. Our work shows that significant molecule association efficiencies can be achieved even for atomic species or mixtures that lack Feshbach resonances suitable for magnetoassociation.

  2. The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development

    NARCIS (Netherlands)

    Geiger, J.C.; Lipka, Joanna; Hoyer, S.; Schlager, M.A.; Wulf, Phebe; Weinges, S.; Demmers, J.; Hoogenraad, Casper

    2014-01-01

    Regulation of cargo transport via adaptor molecules is essential for neuronal development. However, the role of PDZ scaffolding proteins as adaptors in neuronal cargo trafficking is still poorly understood. Here, we show by genetic deletion in mice that the multi-PDZ domain scaffolding protein

  3. 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.

  4. VLT/X-Shooter spectroscopy of the afterglow of the Swift GRB 130606A. Chemical abundances and reionisation at z ~ 6

    Science.gov (United States)

    Hartoog, O. E.; Malesani, D.; Fynbo, J. P. U.; Goto, T.; Krühler, T.; Vreeswijk, P. M.; De Cia, A.; Xu, D.; Møller, P.; Covino, S.; D'Elia, V.; Flores, H.; Goldoni, P.; Hjorth, J.; Jakobsson, P.; Krogager, J.-K.; Kaper, L.; Ledoux, C.; Levan, A. J.; Milvang-Jensen, B.; Sollerman, J.; Sparre, M.; Tagliaferri, G.; Tanvir, N. R.; de Ugarte Postigo, A.; Vergani, S. D.; Wiersema, K.; Datson, J.; Salinas, R.; Mikkelsen, K.; Aghanim, N.

    2015-08-01

    Context. The reionisation of the Universe is a process that is thought to have ended around z ~ 6, as inferred from spectroscopy of distant bright background sources, such as quasars (QSO) and gamma-ray burst (GRB) afterglows. Furthermore, spectroscopy of a GRB afterglow provides insight in its host galaxy, which is often too dim and distant to study otherwise. Aims: For the Swift GRB 130606A at z = 5.913 we have obtained a high S/N spectrum covering the full optical and near-IR wavelength region at intermediate spectral resolution with VLT/X-Shooter. We aim to measure the degree of ionisation of the intergalactic medium (IGM) between z = 5.02-5.84 and to study the chemical abundance pattern and dust content of its host galaxy. Methods: We estimated the UV continuum of the GRB afterglow using a power-law extrapolation, then measured the flux decrement due to absorption at Lyα,β, and γ wavelength regions. Furthermore, we fitted the shape of the red damping wing of Lyα. The hydrogen and metal absorption lines formed in the host galaxy were fitted with Voigt profiles to obtain column densities. We investigated whether ionisation corrections needed to be applied. Results: Our measurements of the Lyα-forest optical depth are consistent with previous measurements of QSOs, but have a much smaller uncertainty. The analysis of the red damping wing yields a neutral fraction xH i 5.6. GRBs are useful probes of the ionisation state of the IGM in the early Universe, but because of internal scatter we need a larger statistical sample to draw robust conclusions. The high [Si/Fe] in the host can be due to dust depletion, α-element enhancement, or a combination of both. The very high value of [ Al/Fe ] = 2.40 ± 0.78 might be due to a proton capture process and is probably connected to the stellar population history. We estimate the host metallicity to be -1.7 Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the

  5. A novel method for evaluating microglial activation using ionized calcium-binding adaptor protein-1 staining : cell body to cell size ratio

    NARCIS (Netherlands)

    Hovens, Iris; Nyakas, Csaba; Schoemaker, Regina

    2014-01-01

    Aim: The aim was to validate a newly developed methodology of semi-automatic image analysis to analyze microglial morphology as marker for microglial activation in ionized calcium-binding adaptor protein-1 (IBA-1) stained brain sections. Methods: The novel method was compared to currently used

  6. Water molecule-enhanced CO2 insertion in lanthanide coordination polymers

    International Nuclear Information System (INIS)

    Luo Liushan; Huang Xiaoyuan; Wang Ning; Wu Hongyan; Chen Wenbin; Feng Zihao; Zhu Huiping; Peng Xiaoling; Li Yongxian; Huang Ling; Yue Shantang; Liu Yingliang

    2009-01-01

    Two new lanthanide coordination polymers H 2 N(CH 3 ) 2 .[Eu III 2 (L 1 ) 3 (L 2 )] (1, L 1 =isophthalic acid dianion, L 2 =formic acid anion) and [La III (2,5-PDC)(L 2 )](2, 2,5-PDC=2,5-pyridinedicarboxylate dianion) were synthesized under solvothermal conditions. It is of interest that the formic ligand (L 2 ) is not contained in the stating materials, but arises from the water molecule-enhanced CO 2 insertion during the solvothermal process. Both of the two compounds exhibit complicated three dimensional sandwich-like frameworks. - Graphical abstract: Two new lanthanide coordination polymers involving water molecule-enhanced CO 2 insertion resulting in the formation of formic anion and dimethylammonium cation were synthesized under solvothermal conditions.

  7. Electron distributions of the first-row homonuclear diatomic molecules, A2

    International Nuclear Information System (INIS)

    Ramirez, B.I.; Bielefeld Univ.

    1982-08-01

    Electron momentum density contour maps of the first-row homonuclear diatomic molecules, A 2 , are obtained from near Hartree-Fock wave functions. Both the total momentum density and momentum density difference (molecule - isolated atoms) maps present trends that may be related to the binding in the molecules. These results are compared with the corresponding charge density maps in position space (Bader, Henneker and Cade 1967). (author)

  8. Increased Level of Phosphorylated ShcA Measured by Chemiluminescence-Linked Immunoassay Is a Predictor of Good Prognosis in Primary Breast Cancer Expressing Low Levels of Estrogen Receptor

    Directory of Open Access Journals (Sweden)

    Serenella Eppenberger-Castori

    2010-03-01

    Full Text Available The SH2 domain-containing adaptor protein ShcA is a proto-oncogene involved in growth factor receptor signaling. The role of phosphorylated ShcA is to link receptor tyrosine kinases with the SH2-containing adaptor protein Grb2, thus facilitating signal transduction from receptor tyrosine kinases to Ras, leading to MAPK activation. The present study was designed to investigate the prognostic significance of phosphorylated ShcA in primary breast cancer and its association in the interactions between the ER and ErbB2 pathways. Using a two-site chemiluminescence-linked immunosorbent assay, we detected the quantitative expression levels of total tyrosine- and threonine-phosphorylated ShcA in cytosol fractions obtained from fresh frozen tissue samples of 153 selected primary breast cancer patients. ShcA phosphorylation was not associated with nodal status, estrogen receptor (ER status or grading. High levels of both tyrosine (pYShcA and serine (pSShcA phosphorylated ShcA correlated with good prognosis (p < 0.01, with respect to both disease-free (DFS and overall survival (OS. In addition, pShcA levels were found to correlate with threonine-phosphorylated ErbB2 and inversely with phosphorylated Akt (pAkt, as well as ErbB2 and ER expression levels. Our findings demonstrate that ShcA activation in primary breast cancer patients correlates with low levels of ER, and is associated with good prognosis.

  9. TLR accessory molecule RP105 (CD180 is involved in post-interventional vascular remodeling and soluble RP105 modulates neointima formation.

    Directory of Open Access Journals (Sweden)

    Jacco C Karper

    Full Text Available BACKGROUND: RP105 (CD180 is TLR4 homologue lacking the intracellular TLR4 signaling domain and acts a TLR accessory molecule and physiological inhibitor of TLR4-signaling. The role of RP105 in vascular remodeling, in particular post-interventional remodeling is unknown. METHODS AND RESULTS: TLR4 and RP105 are expressed on vascular smooth muscle cells (VSMC as well as in the media of murine femoral artery segments as detected by qPCR and immunohistochemistry. Furthermore, the response to the TLR4 ligand LPS was stronger in VSMC from RP105(-/- mice resulting in a higher proliferation rate. In RP105(-/- mice femoral artery cuff placement resulted in an increase in neointima formation as compared to WT mice (4982 ± 974 µm(2 vs.1947 ± 278 µm(2,p = 0.0014. Local LPS application augmented neointima formation in both groups, but in RP105(-/- mice this effect was more pronounced (10316±1243 µm(2 vs.4208 ± 555 µm(2,p = 0.0002, suggesting a functional role for RP105. For additional functional studies, the extracellular domain of murine RP105 was expressed with or without its adaptor protein MD1 and purified. SEC-MALSanalysis showed a functional 22 homodimer formation of the RP105-MD1 complex. This protein complex was able to block the TLR4 response in whole blood ex-vivo. In vivo gene transfer of plasmid vectors encoding the extracellular part of RP105 and its adaptor protein MD1 were performed to initiate a stable endogenous soluble protein production. Expression of soluble RP105-MD1 resulted in a significant reduction in neointima formation in hypercholesterolemic mice (2500 ± 573 vs.6581 ± 1894 µm(2,p<0.05, whereas expression of the single factors RP105 or MD1 had no effect. CONCLUSION: RP105 is a potent inhibitor of post-interventional neointima formation.

  10. Listeriolysin O Regulates the Expression of Optineurin, an Autophagy Adaptor That Inhibits the Growth of Listeria monocytogenes.

    Science.gov (United States)

    Puri, Madhu; La Pietra, Luigi; Mraheil, Mobarak Abu; Lucas, Rudolf; Chakraborty, Trinad; Pillich, Helena

    2017-09-05

    Autophagy, a well-established defense mechanism, enables the elimination of intracellular pathogens including Listeria monocytogenes . Host cell recognition results in ubiquitination of L . monocytogenes and interaction with autophagy adaptors p62/SQSTM1 and NDP52, which target bacteria to autophagosomes by binding to microtubule-associated protein 1 light chain 3 (LC3). Although studies have indicated that L . monocytogenes induces autophagy, the significance of this process in the infectious cycle and the mechanisms involved remain poorly understood. Here, we examined the role of the autophagy adaptor optineurin (OPTN), the phosphorylation of which by the TANK binding kinase 1 (TBK1) enhances its affinity for LC3 and promotes autophagosomal degradation, during L . monocytogenes infection. In LC3- and OPTN-depleted host cells, intracellular replicating L . monocytogenes increased, an effect not seen with a mutant lacking the pore-forming toxin listeriolysin O (LLO). LLO induced the production of OPTN. In host cells expressing an inactive TBK1, bacterial replication was also inhibited. Our studies have uncovered an OPTN-dependent pathway in which L . monocytogenes uses LLO to restrict bacterial growth. Hence, manipulation of autophagy by L . monocytogenes , either through induction or evasion, represents a key event in its intracellular life style and could lead to either cytosolic growth or persistence in intracellular vacuolar structures.

  11. Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS.

    Science.gov (United States)

    Huang, William Y C; Yan, Qingrong; Lin, Wan-Chen; Chung, Jean K; Hansen, Scott D; Christensen, Sune M; Tu, Hsiung-Lin; Kuriyan, John; Groves, Jay T

    2016-07-19

    The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. The generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes.

  12. The Lag-Luminosity Relation in the GRB Source Frame: An Investigation with Swift BAT Bursts

    Science.gov (United States)

    Ukwatta, T. N.; Dhuga, K. S.; Stamatikos, M.; Dermer, C. D.; Sakamoto, T.; Sonbas, E.; Parke, W. C.; Maximon, L. C.; Linnemann, J. T.; Bhat, P. N.; hide

    2011-01-01

    Spectral lag. which is defined as the difference in time of arrival of high- and low-energy photons. is a common feature in gamma-ray bursts (GRBs). Previous investigations have shown a correlation between this lag and the isotropic peak luminosity for long duration bursts. However. most of the previous investigations used lags extracted in the observer frame only. In this work (based on a sample of 43 Swift long GRBs with known redshifts). we present an analysis of the lag-luminosity relation in the GRB source frame. Our analysis indicates a higher degree of correlation -0.82 +/- 0.05 (chance probability of approx. 5.5 x 10(exp -5) between the spectral lag and the isotropic peak luminosity, L(sub iso). with a best-fitting power-law index of -1.2 +/- 0.2. In addition, there is an anticorrelation between the source-frame spectral lag and the source-frame peak energy of the burst spectrum.

  13. 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

  14. 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.

  15. 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.

  16. Essential roles of Gab1 tyrosine phosphorylation in growth factor-mediated signaling and angiogenesis.

    Science.gov (United States)

    Wang, Weiye; Xu, Suowen; Yin, Meimei; Jin, Zheng Gen

    2015-02-15

    Growth factors and their downstream receptor tyrosine kinases (RTKs) mediate a number of biological processes controlling cell function. Adaptor (docking) proteins, which consist exclusively of domains and motifs that mediate molecular interactions, link receptor activation to downstream effectors. Recent studies have revealed that Grb2-associated-binders (Gab) family members (including Gab1, Gab2, and Gab3), when phosphorylated on tyrosine residues, provide binding sites for multiple effector proteins, such as Src homology-2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) and phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, thereby playing important roles in transducing RTKs-mediated signals into pathways with diversified biological functions. Here, we provide an up-to-date overview on the domain structure and biological functions of Gab1, the most intensively studied Gab family protein, in growth factor signaling and biological functions, with a special focus on angiogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. 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).

  18. The (e,2e) reaction in molecules

    International Nuclear Information System (INIS)

    Dey, S.; Dixon, A.; Teubner, P.J.O.; Weigold, E.

    1975-01-01

    The aplication of the (e,2e) technique is discussed in the framework of (e,2e) on molecular hydrogen. It is shown that the technique is sufficiently sensitive to distinguish between simple wavefunctions and those containing configuration interactions. By comparing the data on H 2 and D 2 is shown that the Born-Oppenheimer approximation is confirmed to an accuracy of about 3 per cent. The data is also used to contrast other methods of determining electron momentum distributions in molecules. Data on methane, carbon monoxide and molecular nitrogen is also presented. (author)

  19. Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis: a novel therapeutic target for fatty liver disease.

    Science.gov (United States)

    Chen, Shuai; Kang, Yujia; Sun, Yan; Zhong, Yanhong; Li, Yanli; Deng, Lijuan; Tao, Jin; Li, Yang; Tian, Yingpu; Zhao, Yinan; Cheng, Jianghong; Liu, Wenjie; Feng, Gen-Sheng; Lu, Zhongxian

    2016-12-01

    Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders. The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors. In this study, we investigated the role of a signaling adaptor protein, GRB2-associated-binding protein 2 (Gab2), in fatty liver using an animal disease model. Gab2 expression in hepatocytes responded to various disease factor stimulations, and Gab2 knockout mice exhibited resistance to fat-induced obesity, fat- or alcohol-stimulated hepatic steatosis, as well as methionine and choline deficiency-induced steatohepatitis. Concordantly, the forced expression or knockdown of Gab2 enhanced or diminished oleic acid (OA)- or ethanol-induced lipid production in hepatocytes in vitro, respectively. During lipid accumulation in hepatocytes, both fat and alcohol induced the recruitment of PI3K or Socs3 by Gab2 and the activation of their downstream signaling proteins AKT, ERK, and Stat3. Therefore, Gab2 may be a disease-associated protein that is induced by pathogenic factors to amplify and coordinate multifactor-induced signals to govern disease development in the liver. Our research provides a novel potential target for the prevention and intervention of fatty liver disease. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

  20. Inhibition of tumor metastasis by a growth factor receptor bound protein 2 Src homology 2 domain-binding antagonist.

    Science.gov (United States)

    Giubellino, Alessio; Gao, Yang; Lee, Sunmin; Lee, Min-Jung; Vasselli, James R; Medepalli, Sampath; Trepel, Jane B; Burke, Terrence R; Bottaro, Donald P

    2007-07-01

    Metastasis, the primary cause of death in most forms of cancer, is a multistep process whereby cells from the primary tumor spread systemically and colonize distant new sites. Blocking critical steps in this process could potentially inhibit tumor metastasis and dramatically improve cancer survival rates; however, our understanding of metastasis at the molecular level is still rudimentary. Growth factor receptor binding protein 2 (Grb2) is a widely expressed adapter protein with roles in epithelial cell growth and morphogenesis, as well as angiogenesis, making it a logical target for anticancer drug development. We have previously shown that a potent antagonist of Grb2 Src homology-2 domain-binding, C90, blocks growth factor-driven cell motility in vitro and angiogenesis in vivo. We now report that C90 inhibits metastasis in vivo in two aggressive tumor models, without affecting primary tumor growth rate. These results support the potential efficacy of this compound in reducing the metastatic spread of primary solid tumors and establish a critical role for Grb2 Src homology-2 domain-mediated interactions in this process.