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

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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.

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

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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.

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...

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...

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

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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.

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

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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.

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

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.

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....

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

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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.

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

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

Novel nonphosphorylated peptides with conserved sequences selectively bind to Grb7 SH2 domain with affinity comparable to its phosphorylated ligand.

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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.

Grb2 mediates semaphorin-4D-dependent RhoA inactivation.

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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.

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

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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.

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

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...

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

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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

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

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.

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.

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

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

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.

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

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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.

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.

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.

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

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.

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...

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.

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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.

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

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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.

Constitutive phosphorylation of Shc proteins in human tumors

DEFF Research Database (Denmark)

Pelicci, G; Lanfrancone, L; Salcini, A E

1995-01-01

The Shc gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are ubiquitously expressed and are downstream targets and effectors of activated tyrosine kinases (TK). We investigated tyrosine-phosphorylation of Shc proteins in normal and transformed...... of the Shc-associated phosphoproteins (EGFR, PDGFR, erbB-2, Met, bcr-abl, H4-ret) bound both the Shc- and Grb2-SH2 domains in vitro; others (p175; p70-p80) only the Shc-SH2 domain and yet others (p140) only the Grb2-SH3 domains. These results indicate that Shc proteins are common substrates of constitutively...

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

Directory of Open Access Journals (Sweden)

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

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

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...

Patient-derived Hormone-naive Prostate Cancer Xenograft Models Reveal Growth Factor Receptor Bound Protein 10 as an Androgen Receptor-repressed Gene Driving the Development of Castration-resistant Prostate Cancer.

Science.gov (United States)

Hao, Jun; Ci, Xinpei; Xue, Hui; Wu, Rebecca; Dong, Xin; Choi, Stephen Yiu Chuen; He, Haiqing; Wang, Yu; Zhang, Fang; Qu, Sifeng; Zhang, Fan; Haegert, Anne M; Gout, Peter W; Zoubeidi, Amina; Collins, Colin; Gleave, Martin E; Lin, Dong; Wang, Yuzhuo

2018-06-01

Although androgen deprivation therapy is initially effective in controlling growth of hormone-naive prostate cancers (HNPCs) in patients, currently incurable castration-resistant prostate cancer (CRPC) inevitably develops. To identify CRPC driver genes that may provide new targets to enhance CRPC therapy. Patient-derived xenografts (PDXs) of HNPCs that develop CRPC following host castration were examined for changes in expression of genes at various time points after castration using transcriptome profiling analysis; particular attention was given to pre-CRPC changes in expression indicative of genes acting as potential CRPC drivers. The functionality of a potential CRPC driver was validated via its knockdown in cultured prostate cancer cells; its clinical relevance was established using data from prostate cancer patient databases. Eighty genes were found to be significantly upregulated at the CRPC stage, while seven of them also showed elevated expression prior to CRPC development. Among the latter, growth factor receptor bound protein 10 (GRB10) was the most significantly and consistently upregulated gene. Moreover, elevated GRB10 expression in clinical prostate cancer samples correlated with more aggressive tumor types and poorer patient treatment outcome. GRB10 knockdown markedly reduced prostate cancer cell proliferation and activity of AKT, a well-established CRPC mediator. A positive correlation between AKT activity and GRB10 expression was also found in clinical cohorts. GRB10 acts as a driver of CRPC and sensitizes androgen receptor pathway inhibitors, and hence GRB10 targeting provides a novel therapeutic strategy for the disease. Development of castration-resistant prostate cancer (CRPC) is a major problem in the management of the disease. Using state-of-the-art patient-derived hormone-naive prostate cancer xenograft models, we found and validated the growth factor receptor bound protein 10 gene as a driver of CRPC, indicating that it may be used as a

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

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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.

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.

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

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

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

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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.

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.

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.

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

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

21 CFR 862.1640 - Protein-bound iodine test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Protein-bound iodine test system. 862.1640 Section... Systems § 862.1640 Protein-bound iodine test system. (a) Identification. A protein-bound iodine test system is a device intended to measure protein-bound iodine in serum. Measurements of protein-bound...

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.

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.

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.

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

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

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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.

Twisting, supercoiling and stretching in protein bound DNA

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Lam, Pui-Man; Zhen, Yi

2018-04-01

We have calculated theoretical results for the torque and slope of the twisted DNA, with various proteins bound on it, using the Neukirch-Marko model, in the regime where plectonemes exist. We found that the torque in the protein bound DNA decreases compared to that in the bare DNA. This is caused by the decrease in the free energy g(f) , and hence the smaller persistence lengths, in the case of protein bound DNA. We hope our results will encourage experimental investigations of supercoiling in protein bound DNA, which can provide further tests of the Neukirch-Marko model.

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.

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.

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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

Phosphorylation of the Grb2- and phosphatidylinositol 3-kinase p85-binding p36/38 by Syk in Lck-negative T cells.

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von Willebrand, M; Williams, S; Tailor, P; Mustelin, T

1998-06-01

Activation of the mitogen-activated protein kinase (MAPK) pathway by the T-cell antigen receptor (TCR) in T cells involves a positive role for phosphatidylinositol 3-kinase (PI3K) activity. We recently reported that over-expression of the Syk protein tyrosine kinase in the Lck-negative JCaM1 cells enabled the TCR to induce a normal activation of the Erk2 MAPK and enhanced transcription of a reporter gene driven by the nuclear factor of activated T cells and AP-1. Because this system allows us to analyse the targets for Syk in receptor-mediated signalling, we examined the role of PI3K in signalling events between the TCR-regulated Syk and the downstream activation of Erk2. We report that inhibition of PI3K by wortmannin or an inhibitory p85 construct, p85deltaiSH2, reduced the TCR-induced Syk-dependent activation of Erk2, as well as the appearance of phospho-Erk and phospho-Mek. At the same time, expression of Syk resulted in the activation-dependent phosphorylation of three proteins that bound to the src homology 2 (SH2) domains of PI3K p85. The strongest of these bands had an apparent molecular mass of 36-38 kDa on SDS gels, and it was quantitatively removed from the lysates by adsorption to a fusion protein containing the SH2 domain of Grb2. The appearance of this band was Syk dependent, and it was seen only upon triggering of the TCR complex. Thus, p36/38 was phosphorylated by Syk or a Syk-regulated kinase, and this protein may provide a link to the recruitment and activation of PI3K, as well as to the Ras-MAPK pathway, in TCR-triggered T cells.

Maltose-binding protein enhances secretion of recombinant human granzyme B accompanied by in vivo processing of a precursor MBP fusion protein.

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Benjamin Dälken

Full Text Available BACKGROUND: The apoptosis-inducing serine protease granzyme B (GrB is an important factor contributing to lysis of target cells by cytotoxic lymphocytes. Expression of enzymatically active GrB in recombinant form is a prerequisite for functional analysis and application of GrB for therapeutic purposes. METHODS AND FINDINGS: We investigated the influence of bacterial maltose-binding protein (MBP fused to GrB via a synthetic furin recognition motif on the expression of the MBP fusion protein also containing an N-terminal α-factor signal peptide in the yeast Pichia pastoris. MBP markedly enhanced the amount of GrB secreted into culture supernatant, which was not the case when GrB was fused to GST. MBP-GrB fusion protein was cleaved during secretion by an endogenous furin-like proteolytic activity in vivo, liberating enzymatically active GrB without the need of subsequent in vitro processing. Similar results were obtained upon expression of a recombinant fragment of the ErbB2/HER2 receptor protein or GST as MBP fusions. CONCLUSIONS: Our results demonstrate that combination of MBP as a solubility enhancer with specific in vivo cleavage augments secretion of processed and functionally active proteins from yeast. This strategy may be generally applicable to improve folding and increase yields of recombinant proteins.

Maltose-Binding Protein Enhances Secretion of Recombinant Human Granzyme B Accompanied by In Vivo Processing of a Precursor MBP Fusion Protein

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Dälken, Benjamin; Jabulowsky, Robert A.; Oberoi, Pranav; Benhar, Itai; Wels, Winfried S.

2010-01-01

Background The apoptosis-inducing serine protease granzyme B (GrB) is an important factor contributing to lysis of target cells by cytotoxic lymphocytes. Expression of enzymatically active GrB in recombinant form is a prerequisite for functional analysis and application of GrB for therapeutic purposes. Methods and Findings We investigated the influence of bacterial maltose-binding protein (MBP) fused to GrB via a synthetic furin recognition motif on the expression of the MBP fusion protein also containing an N-terminal α-factor signal peptide in the yeast Pichia pastoris. MBP markedly enhanced the amount of GrB secreted into culture supernatant, which was not the case when GrB was fused to GST. MBP-GrB fusion protein was cleaved during secretion by an endogenous furin-like proteolytic activity in vivo, liberating enzymatically active GrB without the need of subsequent in vitro processing. Similar results were obtained upon expression of a recombinant fragment of the ErbB2/HER2 receptor protein or GST as MBP fusions. Conclusions Our results demonstrate that combination of MBP as a solubility enhancer with specific in vivo cleavage augments secretion of processed and functionally active proteins from yeast. This strategy may be generally applicable to improve folding and increase yields of recombinant proteins. PMID:21203542

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

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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.

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

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 bound on the theory parameter κ as |κ |≲1021 m2 . 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.

SH2/SH3 signaling proteins.

Science.gov (United States)

Schlessinger, J

1994-02-01

SH2 and SH3 domains are small protein modules that mediate protein-protein interactions in signal transduction pathways that are activated by protein tyrosine kinases. SH2 domains bind to short phosphotyrosine-containing sequences in growth factor receptors and other phosphoproteins. SH3 domains bind to target proteins through sequences containing proline and hydrophobic amino acids. SH2 and SH3 domain containing proteins, such as Grb2 and phospholipase C gamma, utilize these modules in order to link receptor and cytoplasmic protein tyrosine kinases to the Ras signaling pathway and to phosphatidylinositol hydrolysis, respectively. The three-dimensional structures of several SH2 and SH3 domains have been determined by NMR and X-ray crystallography, and the molecular basis of their specificity is beginning to be unveiled.

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.

GRB 110731A within the IGC paradigm

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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.

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.

Lysine-Derived Protein-Bound Heyns Compounds in Bakery Products.

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Treibmann, Stephanie; Hellwig, Anne; Hellwig, Michael; Henle, Thomas

2017-12-06

Fructose and dicarbonyl compounds resulting from fructose in heated foods have been linked to pathophysiological pathways of several metabolic disorders. Up to now, very little has been known about the Maillard reaction of fructose in food. Heyns rearrangement compounds (HRCs), the first stable intermediates of the Maillard reaction between amino components and fructose, have not yet been quantitated as protein-bound products in food. Therefore, the HRCs glucosyllysine and mannosyllysine were synthesized and characterized by NMR. Protein-bound HRCs in cookies containing various sugars and in commercial bakery products were quantitated after enzymatic hydrolysis by RP-HPLC-ESI-MS/MS in the multiple reaction monitoring mode through application of the standard addition method. Protein-bound HRCs were quantitated for the first time in model cookies and in commercial bakery products containing honey, banana, and invert sugar syrup. Concentrations of HRCs from 19 to 287 mg/kg were found, which were similar to or exceeded the content of other frequently analyzed Maillard reaction products, such as N-ε-carboxymethyllysine (10-76 mg/kg), N-ε-carboxyethyllysine (2.5-53 mg/kg), and methylglyoxal-derived hydroimidazolone 1 (10-218 mg/kg) in the analyzed cookies. These results show that substantial amounts of HRCs form during food processing. Analysis of protein-bound HRCs in cookies is therefore useful to evaluate the Maillard reaction of fructose.

Detection of protein-protein interactions by ribosome display and protein in situ immobilisation.

Science.gov (United States)

He, Mingyue; Liu, Hong; Turner, Martin; Taussig, Michael J

2009-12-31

We describe a method for identification of protein-protein interactions by combining two cell-free protein technologies, namely ribosome display and protein in situ immobilisation. The method requires only PCR fragments as the starting material, the target proteins being made through cell-free protein synthesis, either associated with their encoding mRNA as ribosome complexes or immobilised on a solid surface. The use of ribosome complexes allows identification of interacting protein partners from their attached coding mRNA. To demonstrate the procedures, we have employed the lymphocyte signalling proteins Vav1 and Grb2 and confirmed the interaction between Grb2 and the N-terminal SH3 domain of Vav1. The method has promise for library screening of pairwise protein interactions, down to the analytical level of individual domain or motif mapping.

Malabsorption of protein bound vitamin B12.

OpenAIRE

Dawson, D W; Sawers, A H; Sharma, R K

1984-01-01

Patients with subnormal serum vitamin B12 concentrations were tested for absorption of protein bound vitamin B12 and compared with controls. Absorption of the protein bound vitamin appeared to decrease with increasing age in healthy subjects. Differences between the result of this test and the result of the Schilling test in patients who had undergone gastric surgery were confirmed; such differences were also seen in some patients who had iron deficiency anaemia, an excessive alcohol intake, ...

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.

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.

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

Fiber-bound nitrogen in gorilla diets: implications for estimating dietary protein intake of primates.

Science.gov (United States)

Rothman, Jessica M; Chapman, Colin A; Pell, Alice N

2008-07-01

Protein is essential for living organisms, but digestibility of crude protein is poorly understood and difficult to predict. Nitrogen is used to estimate protein content because nitrogen is a component of the amino acids that comprise protein, but a substantial portion of the nitrogen in plants may be bound to fiber in an indigestible form. To estimate the amount of crude protein that is unavailable in the diets of mountain gorillas (Gorilla beringei) in Bwindi Impenetrable National Park, Uganda, foods routinely eaten were analyzed to determine the amount of nitrogen bound to the acid-detergent fiber residue. The amount of fiber-bound nitrogen varied among plant parts: herbaceous leaves 14.5+/-8.9% (reported as a percentage of crude protein on a dry matter (DM) basis), tree leaves (16.1+/-6.7% DM), pith/herbaceous peel (26.2+/-8.9% DM), fruit (34.7+/-17.8% DM), bark (43.8+/-15.6% DM), and decaying wood (85.2+/-14.6% DM). When crude protein and available protein intake of adult gorillas was estimated over a year, 15.1% of the dietary crude protein was indigestible. These results indicate that the proportion of fiber-bound protein in primate diets should be considered when estimating protein intake, food selection, and food/habitat quality.

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

International Nuclear Information System (INIS)

Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio; Hazemann, Isabelle; Jenner, Lasse; Urzhumtsev, Alexandre; Gualerzi, Claudio O.; Klaholz, Bruno P.

2013-01-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

Energy Technology Data Exchange (ETDEWEB)

Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

2013-06-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.

Science.gov (United States)

Baltensperger, K; Kozma, L M; Cherniack, A D; Klarlund, J K; Chawla, A; Banerjee, U; Czech, M P

1993-06-25

Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.

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...

Chloroplast protein synthesis: thylakoid bound polysomes synthesize thylakoid proteins

International Nuclear Information System (INIS)

Hurewitz, J.; Jagendorf, A.T.

1986-01-01

Previous work indicated more polysomes bound to pea thylakoids in light than in the dark, in vivo. With isolated intact chloroplasts incubated in darkness, 24 to 74% more RNA was thylakoid-bound at pH 8.3 than at pH 7. Thus the major effect of light in vivo may be due to higher stroma pH. In isolated pea chloroplasts, initiation inhibitors (pactamycin and kanamycin) decreased the extent of RNA binding, and elongation inhibitors (lincomycin and streptomycin) increased it. Thus translation initiation and termination probably control the cycling of bound ribosomes. While only 3 to 6% of total RNA is in bound polysomes the incorporation of 3 H-Leu into thylakoids was proportional to the amount of this bound RNA. When Micrococcal nuclease-treated thylakoids were added to labeled runoff translation products of stroma ribosomes, less than 1% of the label adhered to the added membranes; but 37% of the labeled products made by thylakoid polysomes were bound. These data support the concept that stroma ribosomes are recruited into thylakoid proteins

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.

Oxidation of DNA, proteins and lipids by DOPA, protein-bound DOPA, and related catechol(amine)s

DEFF Research Database (Denmark)

Pattison, David I; Dean, Roger T; Davies, Michael Jonathan

2002-01-01

Incubation of free 3,4-dihydroxyphenylalanine (DOPA), protein-bound DOPA (PB-DOPA) and related catechols with DNA, proteins and lipids has been shown to result in oxidative damage to the target molecule. This article reviews these reactions with particular emphasis on those that occur in the pres......Incubation of free 3,4-dihydroxyphenylalanine (DOPA), protein-bound DOPA (PB-DOPA) and related catechols with DNA, proteins and lipids has been shown to result in oxidative damage to the target molecule. This article reviews these reactions with particular emphasis on those that occur...... in the presence of molecular O(2) and redox-active metal ions (e.g. Fe(3+), Cu(2+), Cr(6+)), which are known to increase the rate of DOPA oxidation. The majority of oxidative damage appears to be mediated by reactive oxygen species (ROS) such as superoxide and HO(.) radicals, though other DOPA oxidation products...

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...

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.

Substrate-Bound Protein Gradients to Study Haptotaxis

Directory of Open Access Journals (Sweden)

Sebastien G. Ricoult

2015-03-01

Full Text Available Cells navigate in response to inhomogeneous distributions of extracellular guidance cues. The cellular and molecular mechanisms underlying migration in response to gradients of chemical cues have been investigated for over a century. Following the introduction of micropipettes and more recently microfluidics for gradient generation, much attention and effort was devoted to study cellular chemotaxis, which is defined as guidance by gradients of chemical cues in solution. Haptotaxis, directional migration in response to gradients of substrate-bound cues, has received comparatively less attention; however it is increasingly clear that in vivo many physiologically relevant guidance proteins – including many secreted cues – are bound to cellular surfaces or incorporated into extracellular matrix and likely function via a haptotactic mechanism. Here, we review the history of haptotaxis. We examine the importance of the reference surface, the surface in contact with the cell that is not covered by the cue, which forms a gradient opposing the gradient of the protein cue and must be considered in experimental designs and interpretation of results. We review and compare microfluidics, contact-printing, light patterning and 3D fabrication to pattern substrate-bound protein gradients in vitro, and focus on their application to study axon guidance. The range of methods to create substrate-bound gradients discussed herein make possible systematic analyses of haptotactic mechanisms. Furthermore, understanding the fundamental mechanisms underlying cell motility will inform bioengineering approaches to program cell navigation and recover lost function.

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.

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.

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.

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.

A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation.

Science.gov (United States)

Dikic, I; Tokiwa, G; Lev, S; Courtneidge, S A; Schlessinger, J

1996-10-10

The mechanisms by which mitogenic G-protein-coupled receptors activate the MAP kinase signalling pathway are poorly understood. Candidate protein tyrosine kinases that link G-protein-coupled receptors with MAP kinase include Src family kinases, the epidermal growth factor receptor, Lyn and Syk. Here we show that lysophosphatidic acid (LPA) and bradykinin induce tyrosine phosphorylation of Pyk2 and complex formation between Pyk2 and activated Src. Moreover, tyrosine phosphorylation of Pyk2 leads to binding of the SH2 domain of Src to tyrosine 402 of Pyk2 and activation of Src. Transient overexpression of a dominant interfering mutant of Pyk2 or the protein tyrosine kinase Csk reduces LPA- or bradykinin-induced activation of MAP kinase. LPA- or bradykinin-induced MAP kinase activation was also inhibited by overexpression of dominant interfering mutants of Grb2 and Sos. We propose that Pyk2 acts with Src to link Gi- and Gq-coupled receptors with Grb2 and Sos to activate the MAP kinase signalling pathway in PC12 cells.

REE bound proteins in natural plant fern Dicranopteris dichitoma by MAA

International Nuclear Information System (INIS)

Guo, F.Q.; Wang, Y.Q.; Sun, J.X.; Chen, H.M.

1996-01-01

Biochemical techniques, including pH variation, outsalting, ultracentrifugation, gel filtration chromatography and electrophoresis, etc., have been employed together with instrumental neutron activation analysis (INAA) to study the rare earth elements (REE) bound proteins in the natural plant fern, Dicranopteris dichitoma. INAA was also used to identify whether the proteins were bound firmly with REE. The results obtained show that two REE bound proteins (RBP-I and RBP-II) have been separated. The molecular weight of RBP-I on Sephadex G-200 gel column is about 8 x 10 5 Daltons and that of RBP-II is less than 12,400 Daltons, respectively. However, SDS-PAGE of the two proteins shows that they mainly have two protein subunits with MW 14,100 and 38,700 Daltons. They are probably conjugated proteins, glycoproteins with different glyco-units. (author). 22 refs., 7 figs., 1 tab

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.

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.

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...

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....

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.

Phosphorylation Regulates the Bound Structure of an Intrinsically Disordered Protein: The p53-TAZ2 Case.

Directory of Open Access Journals (Sweden)

Raúl Esteban Ithuralde

Full Text Available Disordered regions and Intrinsically Disordered Proteins (IDPs are involved in critical cellular processes and may acquire a stable three-dimensional structure only upon binding to their partners. IDPs may follow a folding-after-binding process, known as induced folding, or a folding-before-binding process, known as conformational selection. The transcription factor p53 is involved in the regulation of cellular events that arise upon stress or DNA damage. The p53 domain structure is composed of an N-terminal transactivation domain (p53TAD, a DNA Binding Domain and a tetramerization domain. The activity of TAD is tightly regulated by interactions with cofactors, inhibitors and phosphorylation. To initiate transcription, p53TAD binds to the TAZ2 domain of CBP, a co-transcription factor, and undergoes a folding and binding process, as revealed by the recent NMR structure of the complex. The activity of p53 is regulated by phosphorylation at multiple sites on the TAD domain and recent studies have shown that modifications at three residues affect the binding towards TAZ2. However, we still do not know how these phosphorylations affect the structure of the bound state and, therefore, how they regulate the p53 function. In this work, we have used computational simulations to understand how phosphorylation affects the structure of the p53TAD:TAZ2 complex and regulates the recognition mechanism. Phosphorylation has been proposed to enhance binding by direct interaction with the folded protein or by changing the unbound conformation of IDPs, for example by pre-folding the protein favoring the recognition mechanism. Here, we show an interesting turn in the p53 case: phosphorylation mainly affects the bound structure of p53TAD, highlighting the complexity of IDP protein-protein interactions. Our results are in agreement with previous experimental studies, allowing a clear picture of how p53 is regulated by phosphorylation and giving new insights into how

Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression.

Science.gov (United States)

Schaper, F; Gendo, C; Eck, M; Schmitz, J; Grimm, C; Anhuf, D; Kerr, I M; Heinrich, P C

1998-11-01

Stimulation of the interleukin-6 (IL-6) signalling pathway occurs via the IL-6 receptor-glycoprotein 130 (IL-6R-gp130) receptor complex and results in the regulation of acute-phase protein genes in liver cells. Ligand binding to the receptor complex leads to tyrosine phosphorylation and activation of Janus kinases (Jak), phosphorylation of the signal transducing subunit gp130, followed by recruitment and phosphorylation of the signal transducer and activator of transcription factors STAT3 and STAT1 and the src homology domain (SH2)-containing protein tyrosine phosphatase (SHP2). The tyrosine phosphorylated STAT factors dissociate from the receptor, dimerize and translocate to the nucleus where they bind to enhancer sequences of IL-6 target genes. Phosphorylated SHP2 is able to bind growth factor receptor bound protein (grb2) and thus might link the Jak/STAT pathway to the ras/raf/mitogen-activated protein kinase pathway. Here we present data on the dose-dependence, kinetics and kinase requirements for SHP2 phosphorylation after the activation of the signal transducer, gp130, of the IL-6-type family receptor complex. When human fibrosarcoma cell lines deficient in Jak1, Jak2 or tyrosine kinase 2 (Tyk2) were stimulated with IL-6-soluble IL-6R complexes it was found that only in Jak1-, but not in Jak 2- or Tyk2-deficient cells, SHP2 activation was greatly impaired. It is concluded that Jak1 is required for the tyrosine phosphorylation of SHP2. This phosphorylation depends on Tyr-759 in the cytoplasmatic domain of gp130, since a Tyr-759-->Phe exchange abrogates SHP2 activation and in turn leads to elevated and prolonged STAT3 and STAT1 activation as well as enhanced acute-phase protein gene induction. Therefore, SHP2 plays an important role in acute-phase gene regulation.

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)

MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

Science.gov (United States)

Shelby, Shameka J; Colwill, Karen; Dhe-Paganon, Sirano; Pawson, Tony; Thompson, Debra A

2013-01-01

The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE). A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2)-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999)), purified and phosphorylated. Ni(2+)-NTA pull downs were performed using 6xHis-rMERTK(571-999) in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999) and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α), VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS), siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

MERTK interactions with SH2-domain proteins in the retinal pigment epithelium.

Directory of Open Access Journals (Sweden)

Shameka J Shelby

Full Text Available The receptor tyrosine kinase MERTK plays an essential role in the phagocytic uptake of shed photoreceptor membranes by the retinal pigment epithelium (RPE. A fundamental aspect of signal transduction by receptor tyrosine kinases involves autophosphorylation of tyrosine residues that recruit Src-homology 2 (SH2-domain proteins to the receptor intracellular domain. The goal of the current study was to evaluate the interactions of human MERTK with SH2-domain proteins present in the RPE. The MERTK intracellular domain was expressed as a 6xHis-fusion protein (6xHis-rMERTK(571-999, purified and phosphorylated. Ni(2+-NTA pull downs were performed using 6xHis-rMERTK(571-999 in incubations with recombinant phosphotyrosine-recognition sequences expressed as GST-fusion proteins. In addition, pull downs of native SH2-domain proteins were performed using 6xHis-rMERTK(571-999 and protein homogenates from rat RPE/choroid. For both recombinant and native proteins, western analysis detected MERTK interactions with GRB2, PIK3R1 (P85α, VAV3, and SRC. Immunohistochemical analysis localized each protein to mouse RPE. In cultured RPE-J cells incubated with rod outer segments (OS, siRNA knockdown of Grb2 had no effect on OS binding, but significantly reduced OS uptake. Pik3r1 localized to early phagosomes along with Rab5 and Eea1. Phosphorylation and activation of Src was detected downstream of phagocytosis and Mertk activation. These findings suggest that MERTK signaling in the RPE involves a cohort of SH2-domain proteins with the potential to regulate both cytoskeletal rearrangement and membrane movement. Identification of the SH2-domain signaling partners of MERTK is an important step toward further defining the mechanism of RPE phagocytosis that is central to the function and survival of the retina.

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.

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

The Three-Dimensional Solution Structure of the Src Homology Domain-2 of the Growth Factor Receptor-Bound Protein-2

International Nuclear Information System (INIS)

Senior, Mary M.; Frederick, Anne F.; Black, Stuart; Murgolo, Nicholas J.; Perkins, Louise M.; Wilson, Oswald; Snow, Mark E.; Wang Yusen

1998-01-01

A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NMR data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis. The solution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints. Distance geometry-simulated annealing calculations followed by energy minimization yielded a family of 18 structures that converged to a root-mean-square deviation of 1.09 A for all backbone atoms and 0.40 A for the backbone atoms of the central β-sheet. The core structure of the SH2 domain contains an antiparallel β-sheet flanked by two parallel α-helices displaying an overall architecture that is similar to other known SH2 domain structures. This family of NMR structures is compared to the X-ray structure and to another family of NMR solution structures determined under different solution conditions

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

Protein-Bound Uremic Toxin Profiling as a Tool to Optimize Hemodialysis.

Directory of Open Access Journals (Sweden)

Sunny Eloot

Full Text Available We studied various hemodialysis strategies for the removal of protein-bound solutes, which are associated with cardiovascular damage.This study included 10 patients on standard (3 x 4 h/week high-flux hemodialysis. Blood was collected at the dialyzer inlet and outlet at several time points during a midweek session. Total and free concentration of several protein-bound solutes was determined as well as urea concentration. Per solute, a two-compartment kinetic model was fitted to the measured concentrations, estimating plasmatic volume (V1, total distribution volume (V tot and intercompartment clearance (K21. This calibrated model was then used to calculate which hemodialysis strategy offers optimal removal. Our own in vivo data, with the strategy variables entered into the mathematical simulations, was then validated against independent data from two other clinical studies.Dialyzer clearance K, V1 and V tot correlated inversely with percentage of protein binding. All Ks were different from each other. Of all protein-bound solutes, K21 was 2.7-5.3 times lower than that of urea. Longer and/or more frequent dialysis that processed the same amount of blood per week as standard 3 x 4 h dialysis at 300 mL/min blood flow showed no difference in removal of strongly bound solutes. However, longer and/or more frequent dialysis strategies that processed more blood per week than standard dialysis were markedly more adequate. These conclusions were successfully validated.When blood and dialysate flow per unit of time and type of hemodialyzer are kept the same, increasing the amount of processed blood per week by increasing frequency and/or duration of the sessions distinctly increases removal.

Protein-Bound Uremic Toxin Profiling as a Tool to Optimize Hemodialysis.

Science.gov (United States)

Eloot, Sunny; Schneditz, Daniel; Cornelis, Tom; Van Biesen, Wim; Glorieux, Griet; Dhondt, Annemie; Kooman, Jeroen; Vanholder, Raymond

2016-01-01

We studied various hemodialysis strategies for the removal of protein-bound solutes, which are associated with cardiovascular damage. This study included 10 patients on standard (3 x 4 h/week) high-flux hemodialysis. Blood was collected at the dialyzer inlet and outlet at several time points during a midweek session. Total and free concentration of several protein-bound solutes was determined as well as urea concentration. Per solute, a two-compartment kinetic model was fitted to the measured concentrations, estimating plasmatic volume (V1), total distribution volume (V tot) and intercompartment clearance (K21). This calibrated model was then used to calculate which hemodialysis strategy offers optimal removal. Our own in vivo data, with the strategy variables entered into the mathematical simulations, was then validated against independent data from two other clinical studies. Dialyzer clearance K, V1 and V tot correlated inversely with percentage of protein binding. All Ks were different from each other. Of all protein-bound solutes, K21 was 2.7-5.3 times lower than that of urea. Longer and/or more frequent dialysis that processed the same amount of blood per week as standard 3 x 4 h dialysis at 300 mL/min blood flow showed no difference in removal of strongly bound solutes. However, longer and/or more frequent dialysis strategies that processed more blood per week than standard dialysis were markedly more adequate. These conclusions were successfully validated. When blood and dialysate flow per unit of time and type of hemodialyzer are kept the same, increasing the amount of processed blood per week by increasing frequency and/or duration of the sessions distinctly increases removal.

Protein-bound toxins: added value in their removal with high convective volumes.

Science.gov (United States)

Abad, Soraya; Vega, Almudena; Quiroga, Borja; Arroyo, David; Panizo, Nayara; Reque, Javier Eduardo; López-Gómez, Juan Manuel

Chronic kidney disease is associated with an increased risk of cardiovascular events. In recent years, protein-bound toxins have become more important due to their association with increased morbidity and mortality, characterised by inadequate clearance during dialysis. The purpose of this study is to assess the influence of high convective volumes on postdilution online haemodiafiltration (OL-HDF) on the removal of medium-sized molecules, small molecules and protein-bound molecules. In forty postdilutional OL-HDF sessions, the reduction rates of toxins of different molecular weights were measured in 13 patients, including protein-bound molecules such as p-cresyl sulphate, indoxyl sulphate and homocysteine. Total convective volume was 28.3 (5.1) litres (range 16.3-38.0 litres). Mean reduction rate of protein-bound molecules was 44.4% (15.7%), 48.7% (14.1%) and 58.6% (8.8%) for p-cresyl sulphate, indoxyl sulphate and homocysteine, respectively. Moreover, a statistically significant direct association was found between the reduction rates of all three molecules, the replacement volume and the Kt/V. High convective volumes during postdilution OL-HDF are associated with increased removal of protein-bound uraemic toxins. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Casein kinase II protein kinase is bound to lamina-matrix and phosphorylates lamin-like protein in isolated pea nuclei

Science.gov (United States)

Li, H.; Roux, S. J.

1992-01-01

A casein kinase II (CK II)-like protein kinase was identified and partially isolated from a purified envelope-matrix fraction of pea (Pisum sativum L.) nuclei. When [gamma-32P]ATP was directly added to the envelope-matrix preparation, the three most heavily labeled protein bands had molecular masses near 71, 48, and 46 kDa. Protein kinases were removed from the preparation by sequential extraction with Triton X-100, EGTA, 0.3 M NaCl, and a pH 10.5 buffer, but an active kinase still remained bound to the remaining lamina-matrix fraction after these treatments. This kinase had properties resembling CK II kinases previously characterized from animal and plant sources: it preferred casein as an artificial substrate, could use GTP as efficiently as ATP as the phosphoryl donor, was stimulated by spermine, was calcium independent, and had a catalytic subunit of 36 kDa. Some animal and plant CK II kinases have regulatory subunits near 29 kDa, and a lamina-matrix-bound protein of this molecular mass was recognized on immunoblot by anti-Drosophila CK II polyclonal antibodies. Also found associated with the envelope-matrix fraction of pea nuclei were p34cdc2-like and Ca(2+)-dependent protein kinases, but their properties could not account for the protein kinase activity bound to the lamina. The 71-kDa substrate of the CK II-like kinase was lamin A-like, both in its molecular mass and in its cross-reactivity with anti-intermediate filament antibodies. Lamin phosphorylation is considered a crucial early step in the entry of cells into mitosis, so lamina-bound CK II kinases may be important control points for cellular proliferation.

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)

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).

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.

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.

Study on REE bound proteins in natural plant fern dicranopteris dichotomy by MAA

International Nuclear Information System (INIS)

Guo Fanqing; Wang Yuqi; Sun Jingxing; Chen Hongmin; Xu Lei; Cao Guoyin

1997-01-01

Biochemical techniques, including pH variation, outsalting, ultracentrifugation, gel filtration chromatography and electrophoresis, etc., have been employed together with instrumental neutron activation analysis (INAA) to study the rare earth elements (REE) bound proteins in the natural plant fern, Dicranopteris dichotomy. INAA was also used to identify whether the proteins were bound firmly with REE. The results obtained show that two REE bound proteins (RBP-I and RBP-II) have been separated. The molecular mass (molecular weight, MW) of RBP-I on Sephadex G-200 gel column is about 8 x 10 5 and that of RBP-II is less than 12400, respectively. However, SDS-PAGE of the two proteins shows that they mainly have two protein subunits with MW 14100 and 38700. They are probably conjugated proteins, glycoproteins with different glycol-units

Activated platelet-derived growth factor β receptor and Ras-mitogen-activated protein kinase pathway in natural bovine urinary bladder carcinomas.

Science.gov (United States)

Corteggio, Annunziata; Di Geronimo, Ornella; Roperto, Sante; Roperto, Franco; Borzacchiello, Giuseppe

2012-03-01

Bovine papillomavirus types 1 or 2 (BPV-1/2) are involved in the aetiopathogenesis of bovine urinary bladder cancer. BPV-1/2 E5 activates the platelet-derived growth factor β receptor (PDGFβR). The aim of this study was to analyse the Ras/mitogen-activated protein kinase (MAPK) pathway in relation to activation of PDGFβR in natural bovine urinary bladder carcinomas. Co-immunoprecipitation and Western blot analysis demonstrated that recruitment of growth factor receptor bound protein 2 (GRB-2) and Sos-1 to the activated PDGFβR was increased in carcinomas compared to normal tissues. Higher grade bovine urinary bladder carcinomas were associated with activation of Ras, but not with activation of downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (Mek 1/2) or extracellular signal-regulated kinase (Erk 1/2). Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

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.

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

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.

Nutritional supplements modulate fluorescent protein-bound advanced glycation endproducts and digestive enzymes related to type 2 diabetes mellitus.

Science.gov (United States)

Koch, Emily R; Deo, Permal

2016-09-01

Chronic hyperglycemia enhances the formation of advanced glycation endproducts (AGEs) and reactive oxygen species (ROS), contributing to diabetic complications. Thus, controlling blood glucose levels, inhibiting the formation of AGEs and reducing ROS are key therapeutic targets in early stage type 2 diabetes. The inhibitory effects of seven commercial liquid nutritional supplements against carbohydrate hydrolysing enzymes, α-amylase and α-glucosidase, was determined by dinitrosalicylic (DNS) reagent and p-nitrophenyl-α-D-glucopyranoside solution, respectively. Antiglycation activity was determined using the formation of fluorescent protein-bound AGEs. Total phenolic and flavonoid content and antioxidant properties (1,1-diphenyl-2-picrylhydrazyl antioxidant activity (DPPH) and ferric reducing antioxidant power (FRAP)) were determined for correlation among these components and inhibitory activities. Samoan noni juice showed the greatest inhibitory effects against α-amylase, whereas chlorophyll extracts showed the greatest inhibitory effect against α-glucosidase. Inhibition of α-glucosidase correlated with TFC (r(2) = 0.766; p 1) and FRAP (r(2) = 0.750; p 1) whereas no correlation was observed for α-amylase inhibition. All supplements inhibited fluorescent protein-bound AGEs, with the greatest effect exerted by Olive Leaf Extract, Blood Sugar Support (IC50 = 0.5 mg/ml). The IC50 values negatively correlated with TPC (r(2) = -0.707; p 1) and DPPH scavenging activities (r(2) = 0.515; p nutritional supplements in managing and treating type 2 diabetes mellitus.

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.

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.

Differential Labeling of Free and Disulfide-Bound Thiol Functions in Proteins

NARCIS (Netherlands)

Seiwert, B.; Hayen, H.; Karst, U.

2008-01-01

A method for the simultaneous determination of the number of free cysteine groups and disulfide-bound cysteine groups in proteins has been developed based on the sequential labeling of free and bound thiol functionalities with two ferrocene-based maleimide reagents. Liquid

G protein- and agonist-bound serotonin 5-HT2A receptor model activated by steered molecular dynamics simulations

DEFF Research Database (Denmark)

Ísberg, Vignir; Balle, Thomas; Sander, Tommy

2011-01-01

molecular dynamics (MD) simulations. The driving force for the transformation was the addition of several known intermolecular and receptor interhelical hydrogen bonds enforcing the necessary helical and rotameric movements. Subsquent MD simulations without constraints confirmed the stability......A 5-HT(2A) receptor model was constructed by homology modeling based on the ß(2)-adrenergic receptor and the G protein-bound opsin crystal structures. The 5-HT(2A) receptor model was transferred into an active conformation by an agonist ligand and a G(aq) peptide in four subsequent steered...

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.

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.

Characterization of a major 31-kilodalton peptidoglycan-bound protein of Legionella pneumophila

International Nuclear Information System (INIS)

Butler, C.A.; Hoffman, P.S.

1990-01-01

A 31-kilodalton (kDa) protein was solubilized from the peptidoglycan (PG) fraction of Legionella pneumophila after treatment with either N-acetylmuramidase from the fungus Chalaropsis sp. or with mutanolysin from Streptomyces globisporus. The protein exhibited a ladderlike banding pattern by autoradiography when radiolabeled [(35S]cysteine or [35S]methionine) PG material was extensively treated with hen lysozyme. The banding patterns ranging between 31 and 45 kDa and between 55 and 60 kDa resolved as a single 31-kDa protein when the material was subsequently treated with N-acetylmuramidase. Analysis of the purified 31-kDa protein for diaminopimelic acid by gas chromatography revealed 1 mol of diaminopimelic acid per mol of protein. When outer membrane PG material containing the major outer membrane porin protein was treated with N-acetylmuramidase or mutanolysin, both the 28.5-kDa major outer membrane protein and the 31-kDa protein were solubilized from the PG material under reducing conditions. In the absence of 2-mercaptoethanol, a high-molecular-mass complex (100 kDa) was resolved. The results of this study indicate that a 31-kDa PG-bound protein is a major component of the cell wall of L. pneumophila whose function may be to anchor the major outer membrane protein to PG. Finally, a survey of other Legionella species and other serogroups of L. pneumophila suggested that PG-bound proteins may be a common feature of this genus

Fragment-based modelling of single stranded RNA bound to RNA recognition motif containing proteins

Science.gov (United States)

de Beauchene, Isaure Chauvot; de Vries, Sjoerd J.; Zacharias, Martin

2016-01-01

Abstract Protein-RNA complexes are important for many biological processes. However, structural modeling of such complexes is hampered by the high flexibility of RNA. Particularly challenging is the docking of single-stranded RNA (ssRNA). We have developed a fragment-based approach to model the structure of ssRNA bound to a protein, based on only the protein structure, the RNA sequence and conserved contacts. The conformational diversity of each RNA fragment is sampled by an exhaustive library of trinucleotides extracted from all known experimental protein–RNA complexes. The method was applied to ssRNA with up to 12 nucleotides which bind to dimers of the RNA recognition motifs (RRMs), a highly abundant eukaryotic RNA-binding domain. The fragment based docking allows a precise de novo atomic modeling of protein-bound ssRNA chains. On a benchmark of seven experimental ssRNA–RRM complexes, near-native models (with a mean heavy-atom deviation of <3 Å from experiment) were generated for six out of seven bound RNA chains, and even more precise models (deviation < 2 Å) were obtained for five out of seven cases, a significant improvement compared to the state of the art. The method is not restricted to RRMs but was also successfully applied to Pumilio RNA binding proteins. PMID:27131381

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

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 ...

Nanoscale observation of local bound charges of patterned protein arrays by scanning force microscopy

International Nuclear Information System (INIS)

Oh, Y J; Jo, W; Kim, S; Park, S; Kim, Y S

2008-01-01

A protein patterned surface using micro-contact printing methods has been investigated by scanning force microscopy. Electrostatic force microscopy (EFM) was utilized for imaging the topography and detecting the electrical properties such as the local bound charge distribution of the patterned proteins. It was found that the patterned IgG proteins are arranged down to 1 μm, and the 90 deg. rotation of patterned anti-IgG proteins was successfully undertaken. Through the estimation of the effective areas, it was possible to determine the local bound charges of patterned proteins which have opposite electrostatic force behaviors. Moreover, we studied the binding probability between IgG and anti-IgG in a 1 μm 2 MIMIC system by topographic and electrostatic signals for applicable label-free detections. We showed that the patterned proteins can be used for immunoassay of proteins on the functional substrate, and that they can also be used for bioelectronics device application, indicating distinct advantages with regard to accuracy and a label-free detection

Tumor promoter induced membrane-bound protein kinase C - its influence on hematogenous metastasis

International Nuclear Information System (INIS)

Gopalakrishna, R.; Barsky, S.H.

1987-01-01

A correlation between the amount of membrane-bound detergent-extractable protein kinase C activity in various B16 melanoma sublines (F10, F1, BL6) and their lung metastasizing abilities following intravenous injection was found. The F10 subline which exhibits higher metastasizing ability was found to have higher membrane-bound protein kinase C compared to the lower metastasizing subline, F1. Treatment of F1 cells with 100 nM 12-0 tetradecanoylphorbol-13-acetate (TPA) for 1h resulted in 90% decrease in protein kinase C activity in the cytosol with a concommitent increase in membrane-bound activity. These TPA-treated cells when injected intravenously in C57BL/6 mice produced 6-fold increase in pulmonary metastases compared to untreated F1 cells. However, biologically inactive analogues 4 α-phorbol 12,13-didecanoate and phorbol 13-acetate had no effect on either membrane-bound protein kinase C activity or pulmonary metastases. Treating F1 cells with the second-stage tumor promoter, mezerin, resulted in increase in both membrane association of protein kinase C and also lung metastases. Thus, these results strongly suggests that membrane associated protein kinase C activity influences hematogenous metastasis of these melanoma cells

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...

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...

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.

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...

TUNABLE TENSOR VOTING FOR REGULARIZING PUNCTATE PATTERNS OF MEMBRANE-BOUND PROTEIN SIGNALS

OpenAIRE

Loss, Leandro

2009-01-01

Membrane-bound protein, expressed in the basal-lateral region, is heterogeneous and an important endpoint for understanding biological processes. At the optical resolution, membrane-bound protein can be visualized as being diffused (e.g., E-cadherin), punctate (e.g., connexin), or simultaneously diffused and punctate as a result of sample preparation or conditioning. Furthermore, there is a significant amount of heterogeneity as a result of technical and biological variations. This paper aims...

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.

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.;

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.

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...

Identification of peptides from foot‐and‐mouth disease virus structural proteins bound by class I swine leukocyte antigen (SLA) alleles, SLA‐1*0401 and SLA‐2*0401

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Harndahl, M.; Nielsen, Morten

2013-01-01

within the structural proteins of foot‐and‐mouth disease virus (FMDV), strain A24 were analyzed as candidate T‐cell epitopes. Peptides predicted by the NetMHCpan were tested in ELISA for binding to the SLA‐1*0401 and SLA‐2*0401 major histocompatibility complex class I proteins. Four of the 10 predicted...... FMDV peptides bound to SLA‐2*0401, whereas five of the nine predicted FMDV peptides bound to SLA‐1*0401. These methods provide the characterization of T‐cell epitopes in response to pathogens in more detail. The development of such approaches to analyze vaccine performance will contribute to a more...

Speciation of protein-bound trace elements by gel electrophoresis and atomic spectrometry.

Science.gov (United States)

Ma, Renli; McLeod, Cameron W; Tomlinson, Kerry; Poole, Robert K

2004-08-01

The metabolism of trace elements, in particular their binding to proteins in biological systems is of great importance in biochemical, toxicological, and pharmacological studies. As a result there has been a sustained interest over the last two decades in the speciation of protein-bound metals. Various analytical approaches have been employed, combining efficient separation of metalloproteins by liquid chromatography or electrophoresis with high-sensitivity elemental detection. Slab-gel electrophoresis (GE) is a key platform for high-resolution protein separation, and has been combined with autoradiography and various atomic spectrometric techniques for in-gel determination of protein-bound metals. Recently, the combination of GE with state-of-the-art inductively coupled plasma-mass spectrometry (ICP-MS), particularly when linked to laser ablation (LA) for direct gel interrogation, has opened up new opportunities for rapid characterization of metalloproteins. The use of GE and atomic spectrometry for the speciation of protein-bound trace elements is reviewed in this paper. Technical requirements for gel electrophoresis/atomic spectrometric measurement are considered in terms of method compatibilities, detection capability and potential usefulness. The literature is also surveyed to illustrate current status and future trends. Copyright 2004 Wiley-VCH Verlag GmbH and Co.

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.

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

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.

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.

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.

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...

Spermidine is bound to a unique protein in early sea urchin embryos

International Nuclear Information System (INIS)

Canellakis, Z.N.; Bondy, P.K.; Infante, A.A.

1985-01-01

Spermidine is rapidly taken up and becomes bound to protein during the very early hours of sea urchin embryogenesis. During the first 6 hr after fertilization of freshly obtained sea urchin eggs (Strongylocentrotus purpuratus), which are incubated in the presence of exogenous [ 3 H]-spermidine, up to 7% of the total cell-associated spermidine appears uniquely as spermidine bound in macromolecular form. This unique protein containing spermidine migrates as a single radioactive band in gel electrophoresis. It has a Mr of approximately equal to 30,000 and is readily distinguishable from the protein initiation factor eIF-4D, which has a Mr of 18,000, the only other identifiable protein known to date to be posttranslationally modified by polyamines

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...

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...

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.

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.

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.

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.

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

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).

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.

Membrane-bound 2,3-diphosphoglycerate phosphatase of human erythrocytes.

Science.gov (United States)

Schröter, W; Neuvians, M

1970-12-01

Gradual osmotic hemolysis of human erythrocytes reduces the cell content of whole protein, hemoglobin, 2,3-diphosphoglycerate and triosephosphate isomerase extensively, but not that of membrane protein and 2,3-diphosphoglycerate phosphatase. After the refilling of the ghosts with 2,3-diphosphoglycerate and reconstitution of the membrane, the 2,3-diphosphoglycerate phosphatase activity equals that of intact red cells. The membrane-bound 2,3-diphosphoglycerate phosphatase can be activated by sodium hyposulfite. The enzyme system of ghosts seems to differ from that of intact red cells with regard to the optima of pH and temperature. It remains to be elucidated if the membrane binding of the 2,3-diphosphoglycerate phosphatase is related to the transfer of inorganic phosphate across the red cell membrane.

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.

Dynamic nuclear polarization of membrane proteins: covalently bound spin-labels at protein–protein interfaces

International Nuclear Information System (INIS)

Wylie, Benjamin J.; Dzikovski, Boris G.; Pawsey, Shane; Caporini, Marc; Rosay, Melanie; Freed, Jack H.; McDermott, Ann E.

2015-01-01

We demonstrate that dynamic nuclear polarization of membrane proteins in lipid bilayers may be achieved using a novel polarizing agent: pairs of spin labels covalently bound to a protein of interest interacting at an intermolecular interaction surface. For gramicidin A, nitroxide tags attached to the N-terminal intermolecular interface region become proximal only when bimolecular channels forms in the membrane. We obtained signal enhancements of sixfold for the dimeric protein. The enhancement effect was comparable to that of a doubly tagged sample of gramicidin C, with intramolecular spin pairs. This approach could be a powerful and selective means for signal enhancement in membrane proteins, and for recognizing intermolecular interfaces

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.

Protein-bound homocyst(e)ine. A possible risk factor for coronary artery disease.

Science.gov (United States)

Kang, S S; Wong, P W; Cook, H Y; Norusis, M; Messer, J V

1986-01-01

The development of atherosclerotic changes and thromboembolism are common features in homocystinurics. Hence, we postulate a positive correlation between the level of homocyst(e)ine in the blood and the occurrence of coronary artery disease. Homocysteine is found either as free homocystine, cysteine-homocysteine mixed disulfide, or protein-bound homocyst(e)ine. In nonhomocystinuric subjects, most homocysteine molecules are detectable in the protein-bound form. Thus, protein-bound homocyst(e)ine in stored plasma which reflected total plasma homocyst(e)ine was determined in 241 patients with coronary artery disease (173 males and 68 females). The mean +/- SD total plasma homocyst(e)ine was 5.41 +/- 1.62 nmol/ml in male patients, 4.37 +/- 1.09 nmol/ml in male controls, 5.66 +/- 1.93 nmol/ml in female patients, and 4.16 +/- 1.62 nmol/ml in female controls. The differences between the patients with coronary artery disease and the controls were statistically significant (P less than 0.0005). PMID:3700650

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...

UVA photolysis using the protein-bound sensitizers present in human lens

International Nuclear Information System (INIS)

Ortwerth, B.J.; Olesen, P.R.

1994-01-01

This research was undertaken to demonstrate that the protein-bound chromophores in aged human lens can act as sensitizers for protein damage by UVA light. The water-insoluble (WI) proteins from pooled human and bovine lenses were solubilized by sonication in water and illuminated with UV light similar in output to that transmitted by the cornea. Analysis of the irradiated proteins showed a linear decrease in sulfhydryl groups with a 30% loss after 2 h. No loss was seen when native α-crystallin was irradiated under the same conditions. A 25% loss of histidine residues was also observed with the human lens WI fraction, and sodium dodecyl sulfate polyacrylamide gels indicated considerable protein cross-linking. Similar photodamage was seen with a WI fraction from old bovine lenses. While the data show the presence of UVA sensitizers, some histidine destruction and protein cross-linking were also obtained with α-crystallin and with lysozyme which argue that part of the histidine loss in the human WISS was likely due to tryptophan acting as a sensitizer. (Author)

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...

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.

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.

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)

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

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 ...

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.

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.

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.

Unique Pattern of Protein-Bound Maillard Reaction Products in Manuka (Leptospermum scoparium) Honey.

Science.gov (United States)

Hellwig, Michael; Rückriemen, Jana; Sandner, Daniel; Henle, Thomas

2017-05-03

As a unique feature, honey from the New Zealand manuka tree (Leptospermum scoparium) contains substantial amounts of dihydroxyacetone (DHA) and methylglyoxal (MGO). Although MGO is a reactive intermediate in the Maillard reaction, very little is known about reactions of MGO with honey proteins. We hypothesized that the abundance of MGO should result in a particular pattern of protein-bound Maillard reaction products (MRPs) in manuka honey. A protein-rich high-molecular-weight fraction was isolated from 12 manuka and 8 non-manuka honeys and hydrolyzed enzymatically. By HPLC-MS/MS, 8 MRPs, namely, N-ε-fructosyllysine, N-ε-maltulosyllysine, carboxymethyllysine, carboxyethyllysine (CEL), pyrraline, formyline, maltosine, and methylglyoxal-derived hydroimidazolone 1 (MG-H1), were quantitated. Compared to non-manuka honeys, the manuka honeys were characterized by high concentrations of CEL and MG-H1, whereas the formation of N-ε-fructosyllysine was suppressed, indicating concurrence reactions of glucose and MGO at the ε-amino group of protein-bound lysine. Up to 31% of the lysine and 8% of the arginine residues, respectively, in the manuka honey protein can be modified to CEL and MG-H1, respectively. CEL and MG-H1 concentrations correlated strongly with the MGO concentration of the honeys. Manuka honey possesses a special pattern of protein-bound MRPs, which might be used to prove the reliability of labeled MGO levels in honeys and possibly enable the detection of fraudulent MGO or DHA addition to honey.

A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.

Science.gov (United States)

Sellers, W R; Rodgers, J W; Kaelin, W G

1995-01-01

An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor. Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest. In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter. These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F. Images Fig. 4 Fig. 5 PMID:8524800

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.

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

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

Physicochemical characterization of mineral (iron/zinc) bound caseinate and their mineral uptake in Caco-2 cells.

Science.gov (United States)

Shilpashree, B G; Arora, Sumit; Kapila, Suman; Sharma, Vivek

2018-08-15

Milk proteins (especially caseins) are widely accepted as good vehicle for the delivery of various bioactive compounds including minerals. Succinylation is one of the most acceptable chemical modification techniques to enhance the mineral binding ability of caseins. Addition of minerals to succinylated proteins may alter their physicochemical and biochemical properties. Physicochemical characteristics of succinylated sodium caseinate (S.NaCN)-mineral (iron/zinc) complexes were elucidated. Chromatographic behaviour and fluorescence intensity confirmed the structural modification of S.NaCN upon binding with minerals. The bound mineral from protein complexes showed significantly higher (P < 0.05) in vitro bioavailability (mineral uptake) than mineral salts in Caco-2 cells. Also, iron bound S.NaCN showed higher cellular ferritin formation than iron in its free form. These mineral bound protein complexes with improved bioavailability could safely replace inorganic fortificants in various functional food formulations. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Fluorescence detection of a protein-bound 2Fe2S cluster.

Science.gov (United States)

Hoff, Kevin G; Goodlitt, Rochelle; Li, Rui; Smolke, Christina D; Silberg, Jonathan J

2009-03-02

A fluorescent biosensor is described for 2Fe2S clusters that is composed of green fluorescent protein (GFP) fused to glutaredoxin 2 (Grx2), as illustrated here. 2Fe2S detection is based on the reduction of GFP fluorescence upon the 2Fe2S-induced dimerization of GFP-Grx2. This assay is sufficiently sensitive to detect submicromolar changes in 2Fe2S levels, thus making it suitable for high-throughput measurements of metallocluster degradation and synthesis reactions.

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

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.

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.

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

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.

Cartilage Acidic Protein 2 a hyperthermostable, high affinity calcium-binding protein.

Science.gov (United States)

Anjos, Liliana; Gomes, Ana S; Melo, Eduardo P; Canário, Adelino V; Power, Deborah M

2013-03-01

Cartilage Acidic Protein 2 (CRTAC2) is a novel protein present from prokaryotes to vertebrates with abundant expression in the teleost fish pituitary gland and an isoform of CRTAC1, a chondrocyte marker in humans. The two proteins are non-integrins containing N-terminal integrin-like Ca(2+)-binding motifs and their structure and function remain to be assigned. Structural studies of recombinant sea bream (sb)CRTAC2 revealed it is composed of 8.8% α-helix, 33.4% β-sheet and 57.8% unordered protein. sbCRTAC2 bound Ca(2+) with high affinity (K(d)=1.46nM) and favourable Gibbs free energy (∆G=-12.4kcal/mol). The stoichiometry for Ca(2+) bound to sbCRTAC2 at saturation indicated six Ca(2+) ligand-binding sites exist per protein molecule. No conformational change in sbCRTAC2 occurred in the presence of Ca(2+). Fluorescence emission revealed that the tertiary structure of the protein is hyperthermostable between 25°C and 95°C and the fully unfolded state is only induced by chemical denaturing (4M GndCl). sbCRTAC has a widespread tissue distribution and is present as high molecular weight aggregates, although strong reducing conditions promote formation of the monomer. sbCRTAC2 promotes epithelial cell outgrowth in vitro suggesting it may share functional homology with mammalian CRTAC1, recently implicated in cell-cell and cell-matrix interactions. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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.

Myeloperoxidase-mediated protein lysine oxidation generates 2-aminoadipic acid and lysine nitrile in vivo.

Science.gov (United States)

Lin, Hongqiao; Levison, Bruce S; Buffa, Jennifer A; Huang, Ying; Fu, Xiaoming; Wang, Zeneng; Gogonea, Valentin; DiDonato, Joseph A; Hazen, Stanley L

2017-03-01

Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2-AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or base-catalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate protein-bound 2-AAA from an alternative potential lysine oxidative product, lysine nitrile (LysCN). Using a validated protease-based digestion method coupled with stable isotope dilution LC/MS/MS, we now report protein bound 2-AAA and LysCN are both formed by hypochlorous acid (HOCl) and the MPO/H 2 O 2 /Cl - system of leukocytes. At low molar ratio of oxidant to target protein N ε -lysine moiety, 2-AAA is formed via an initial N ε -monochloramine intermediate, which ultimately produces the more stable 2-AAA end-product via sequential generation of transient imine and semialdehyde intermediates. At higher oxidant to target protein N ε -lysine amine ratios, protein-bound LysCN is formed via initial generation of a lysine N ε -dichloramine intermediate. In studies employing MPO knockout mice and an acute inflammation model, we show that both free and protein-bound 2-AAA, and in lower yield, protein-bound LysCN, are formed by MPO in vivo during inflammation. Finally, both 2-AAA and to lesser extent LysCN are shown to be enriched in human aortic atherosclerotic plaque, a tissue known to harbor multiple MPO-catalyzed protein oxidation products. Collectively, these results show that MPO-mediated oxidation of protein lysyl

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.

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 ...

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.

Effects of amantadine on the dynamics of membrane-bound influenza A M2 transmembrane peptide studied by NMR relaxation

Energy Technology Data Exchange (ETDEWEB)

Cady, Sarah D.; Hong Mei [Iowa State University, Department of Chemistry (United States)], E-mail: mhong@iastate.edu

2009-09-15

The molecular motions of membrane proteins in liquid-crystalline lipid bilayers lie at the interface between motions in isotropic liquids and in solids. Specifically, membrane proteins can undergo whole-body uniaxial diffusion on the microsecond time scale. In this work, we investigate the {sup 1}H rotating-frame spin-lattice relaxation (T{sub 1{rho}}) caused by the uniaxial diffusion of the influenza A M2 transmembrane peptide (M2TMP), which forms a tetrameric proton channel in lipid bilayers. This uniaxial diffusion was proved before by {sup 2}H, {sup 15}N and {sup 13}C NMR lineshapes of M2TMP in DLPC bilayers. When bound to an inhibitor, amantadine, the protein exhibits significantly narrower linewidths at physiological temperature. We now investigate the origin of this line narrowing through temperature-dependent {sup 1}H T{sub 1{rho}} relaxation times in the absence and presence of amantadine. Analysis of the temperature dependence indicates that amantadine decreases the correlation time of motion from 2.8 {+-} 0.9 {mu}s for the apo peptide to 0.89 {+-} 0.41 {mu}s for the bound peptide at 313 K. Thus the line narrowing of the bound peptide is due to better avoidance of the NMR time scale and suppression of intermediate time scale broadening. The faster diffusion of the bound peptide is due to the higher attempt rate of motion, suggesting that amantadine creates better-packed and more cohesive helical bundles. Analysis of the temperature dependence of ln (T{sub 1{rho}}{sup -1}) indicates that the activation energy of motion increased from 14.0 {+-} 4.0 kJ/mol for the apo peptide to 23.3 {+-} 6.2 kJ/mol for the bound peptide. This higher activation energy indicates that excess amantadine outside the protein channel in the lipid bilayer increases the membrane viscosity. Thus, the protein-bound amantadine speeds up the diffusion of the helical bundles while the excess amantadine in the bilayer increases the membrane viscosity.

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.

Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application

Science.gov (United States)

Dancik, Yuri; Anissimov, Yuri G; Jepps, Owen G; Roberts, Michael S

2012-01-01

AIMS To relate the varying dermal, subcutaneous and muscle microdialysate concentrations found in man after topical application to the nature of the drug applied and to the underlying physiology. METHODS We developed a physiologically based pharmacokinetic model in which transport to deeper tissues was determined by tissue diffusion, blood, lymphatic and intersitial flow transport and drug properties. The model was applied to interpret published human microdialysis data, estimated in vitro dermal diffusion and protein binding affinity of drugs that have been previously applied topically in vivo and measured in deep cutaneous tissues over time. RESULTS Deeper tissue microdialysis concentrations for various drugs in vivo vary widely. Here, we show that carriage by the blood to the deeper tissues below topical application sites facilitates the transport of highly plasma protein bound drugs that penetrate the skin, leading to rapid and significant concentrations in those tissues. Hence, the fractional concentration for the highly plasma protein bound diclofenac in deeper tissues is 0.79 times that in a probe 4.5 mm below a superficial probe whereas the corresponding fractional concentration for the poorly protein bound nicotine is 0.02. Their corresponding estimated in vivo lag times for appearance of the drugs in the deeper probes were 1.1 min for diclofenac and 30 min for nicotine. CONCLUSIONS Poorly plasma protein bound drugs are mainly transported to deeper tissues after topical application by tissue diffusion whereas the transport of highly plasma protein bound drugs is additionally facilitated by convective blood, lymphatic and interstitial transport to deep tissues. PMID:21999217

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.

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

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

Measuring binding of protein to gel-bound ligands using magnetic levitation.

Science.gov (United States)

Shapiro, Nathan D; Mirica, Katherine A; Soh, Siowling; Phillips, Scott T; Taran, Olga; Mace, Charles R; Shevkoplyas, Sergey S; Whitesides, George M

2012-03-28

This paper describes the use of magnetic levitation (MagLev) to measure the association of proteins and ligands. The method starts with diamagnetic gel beads that are functionalized covalently with small molecules (putative ligands). Binding of protein to the ligands within the bead causes a change in the density of the bead. When these beads are suspended in a paramagnetic aqueous buffer and placed between the poles of two NbFeB magnets with like poles facing, the changes in the density of the bead on binding of protein result in changes in the levitation height of the bead that can be used to quantify the amount of protein bound. This paper uses a reaction-diffusion model to examine the physical principles that determine the values of rate and equilibrium constants measured by this system, using the well-defined model system of carbonic anhydrase and aryl sulfonamides. By tuning the experimental protocol, the method is capable of quantifying either the concentration of protein in a solution, or the binding affinities of a protein to several resin-bound small molecules simultaneously. Since this method requires no electricity and only a single piece of inexpensive equipment, it may find use in situations where portability and low cost are important, such as in bioanalysis in resource-limited settings, point-of-care diagnosis, veterinary medicine, and plant pathology. It still has several practical disadvantages. Most notably, the method requires relatively long assay times and cannot be applied to large proteins (>70 kDa), including antibodies. The design and synthesis of beads with improved characteristics (e.g., larger pore size) has the potential to resolve these problems.

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).

Ligand-free, protein-bound technetium-99m. Evidence for tumour localisation

International Nuclear Information System (INIS)

Jakovljevic, A.C.; Pojer, P.M.

1984-11-01

An hypothesis that cations accumulate in tumours independent of ligand is tested. A preparation of technetium-99m known to be ligand-free (that is, the technetium is protein bound and no other ligand is injected) has been shown to accumulate in a T-cell lymphoma

How to calculate clearance of highly protein-bound drugs during continuous venovenous hemofiltration demonstrated with flucloxacillin.

Science.gov (United States)

Meyer, Brigitte; Ahmed el Gendy, Salwa; Delle Karth, Georg; Locker, Gottfried J; Heinz, Gottfried; Jaeger, Walter; Thalhammer, Florian

2003-01-01

Flucloxacillin is an important antimicrobial drug in the treatment of infections with Staphylococcus aureus and therefore is often used in staphylococcal infections. Furthermore, flucloxacillin has a high protein binding rate as for example ceftriaxone or teicoplanin--drugs which have formerly been characterized as not being dialyzable. The pharmacokinetic parameters of 4.0 g flucloxacillin every 8 h were examined in 10 intensive care patients during continuous venovenous hemofiltration (CVVH) using a polyamide capillary hemofilter. In addition, the difficulty of calculating the hemofiltration clearance of a highly protein-bound drug is described. Flucloxacillin serum levels were significantly lowered (56.9 +/- 24.0%) even though only 15% of the drug was detected in the ultrafiltrate. Elimination half-life, total body clearance and sieving coefficient were 4.9 +/- 0.7 h, 117.2 +/- 79.1 ml/min and 0.21 +/- 0.09, respectively. These discrepancies can be explained by the high protein binding of flucloxacillin, the adsorbing property of polyamide and the equation in order to calculate hemofiltration clearance. The unbound fraction of a 4.0 g flucloxacillin dosage facilitates time above the minimum inhibitory concentration (T > MIC) of 60% only for strains up to a minimum inhibitory concentration (MIC) of 0.5 mg/l. Based on the data of this study, we conclude that intensive care patients with staphylococcal infections on CVVH should be treated with 4.0 g flucloxacillin every 8 h which was safe and well tolerated. Moreover, further studies with highly protein-bound drugs are recommended to check the classical 'hemodialysis' equation as the standard equation in calculating the CVVH clearance of highly protein-bound drugs. Copyright 2003 S. Karger AG, Basel

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

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.

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.

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.

Photochemistry of triarylmethane dyes bound to proteins

Science.gov (United States)

Indig, Guilherme L.

1996-04-01

Triarylmethanes represent a class of cationic dyes whose potential as photosensitizers for use in photodynamic therapy of neoplastic diseases has never been comprehensively evaluated. Here, the laser-induced photodecomposition of three triarylmethane dyes, crystal violet, ethyl violet, and malachite green, non-covalently bound to bovine serum albumin (a model biological target) was investigated. Upon laser excitation at 532 nm, the bleaching of the corresponding dye-protein molecular complexes follows spectroscopic patterns that suggest the formation of reduced forms of the dyes as major reaction photoproducts. That implies that an electron or hydrogen atom transfer from the protein to the dye's moiety within the guest-host complex is the first step of the photobleaching process. Since the availability of dissolved molecular oxygen was not identified as a limiting factor for the phototransformations to occur, these dyes can be seen as potential phototherapeutic agents for use in hypoxic areas of tumors. These triarylmethane dyes strongly absorb at relatively long wavelengths (absorption maximum around 600 nm; (epsilon) max approximately equals 105 M-1 cm-1), and only minor changes in their absorption characteristics are observed upon binding to the protein. However the binding event leads to a remarkable increase in their fluorescence quantum yield and photoreactivity.

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.

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...

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....

The Fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation.

Science.gov (United States)

Sun, X J; Pons, S; Asano, T; Myers, M G; Glasheen, E; White, M F

1996-05-03

Irs-proteins link the receptors for insulin/IGF-1, growth hormones, and several interleukins and interferons to signaling proteins that contain Src homology-2 (SH2). To identify new Irs-1-binding proteins, we screened a mouse embryo expression library with recombinant [32P]Irs-1, which revealed a specific association between p59fyn and Irs-1. The SH2 domain in p59fyn bound to phosphorylated Tyr895 and Tyr1172, which are located in YXX(L/I) motifs. Mutation of p59fyn at the COOH-terminal tyrosine phosphorylation site (Tyr531) enhanced its binding to Irs-1 during insulin stimulation. Binding experiments with various SH2 protein revealed that Grb-2 was largely excluded from Irs-1 complexes containing p59fyn, whereas Grb-2 and p85 occurred in the same Irs-1 complex. By comparison with the insulin receptor, p59fyn kinase phosphorylated a unique cohort of tyrosine residues in Irs-1. These results outline a role for p59fyn or other related Src-kinases during insulin and cytokine signaling.

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.

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.

In Situ Proteolysis for Crystallization of Membrane Bound Cytochrome P450 17A1 and 17A2 Proteins from Zebrafish.

Science.gov (United States)

Lei, Li; Egli, Martin

2016-04-01

Fish and human cytochrome P450 (P450) 17A1 catalyze both steroid 17α-hydroxylation and 17α,20-lyase reactions. Fish P450 17A2 catalyzes only 17α-hydroxylation. Both enzymes are microsomal-type P450s, integral membrane proteins that bind to the membrane through their N-terminal hydrophobic segment, the signal anchor sequence. The presence of this N-terminal region renders expression of full-length proteins challenging or impossible. For some proteins, variable truncation of the signal anchor sequence precludes expression or results in poor expression levels. To crystallize P450 17A1 and 17A2 in order to gain insight into their different activities, we used an alternative N-terminal sequence to boost expression together with in situ proteolysis. Key features of our approach to identify crystallizable P450 fragments were the use of an N-terminal leader sequence, a screen composed of 12 proteases to establish optimal cleavage, variations of protease concentration in combination with an SDS-PAGE assay, and analysis of the resulting fragments using Edman sequencing. Described in this unit are protocols for vector preparation, expression, purification, and in situ proteolytic crystallization of two membrane-bound P450 proteins. Copyright © 2016 John Wiley & Sons, Inc.

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...

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

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

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.

Sex-related differences in gene expression in human skeletal muscle.

Directory of Open Access Journals (Sweden)

Stephen Welle

2008-01-01

Full Text Available There is sexual dimorphism of skeletal muscle, the most obvious feature being the larger muscle mass of men. The molecular basis for this difference has not been clearly defined. To identify genes that might contribute to the relatively greater muscularity of men, we compared skeletal muscle gene expression profiles of 15 normal men and 15 normal women by using comprehensive oligonucleotide microarrays. Although there were sex-related differences in expression of several hundred genes, very few of the differentially expressed genes have functions that are obvious candidates for explaining the larger muscle mass of men. The men tended to have higher expression of genes encoding mitochondrial proteins, ribosomal proteins, and a few translation initiation factors. The women had >2-fold greater expression than the men (P<0.0001 of two genes that encode proteins in growth factor pathways known to be important in regulating muscle mass: growth factor receptor-bound 10 (GRB10 and activin A receptor IIB (ACVR2B. GRB10 encodes a protein that inhibits insulin-like growth factor-1 (IGF-1 signaling. ACVR2B encodes a myostatin receptor. Quantitative RT-PCR confirmed higher expression of GRB10 and ACVR2B genes in these women. In an independent microarray study of 10 men and 9 women with facioscapulohumeral dystrophy, women had higher expression of GRB10 (2.7-fold, P<0.001 and ACVR2B (1.7-fold, P<0.03. If these sex-related differences in mRNA expression lead to reduced IGF-1 activity and increased myostatin activity, they could contribute to the sex difference in muscle size.

Comparative LC-MS/MS profiling of free and protein-bound early and advanced glycation-induced lysine modifications in dairy products

International Nuclear Information System (INIS)

Hegele, Joerg; Buetler, Timo; Delatour, Thierry

2008-01-01

Free and protein-bound forms of early and advanced glycation-induced lysine (Lys) modifications were quantified in dairy products by LC-MS/MS using a stable isotope dilution assay. The glycation profiles for N ε -fructoselysine (FL), N ε -carboxymethyllysine (CML) and pyrraline (Pyr) were monitored in raw and processed cow milk to investigate whether free glycation products could serve as fast and simple markers to assess the extent of protein glycation in dairy products. In all milk samples, the fraction of free glycation adducts was predominantly composed of advanced modifications, e.g. 8.34 ± 3.81 nmol CML per μmol of free Lys (Lys free ) and 81.5 ± 87.8 nmol Pyr μmol -1 Lys free -1 vs. 3.72 ± 1.29 nmol FL μmol -1 Lys free -1 . In contrast, the protein-bound early glycation product FL considerably outweighed the content of CML and Pyr in milk proteins of raw and processed cow milk, whereas severely heat treated milk products, e.g. condensed milk, contained a higher amount of protein-bound advanced glycation adducts. Typical values recorded for milk samples processed under mild conditions were 0.47 ± 0.08 nmol FL μmol -1 of protein-bound Lys (Lys p-b ), 0.04 ± 0.03 nmol CML μmol -1 Lys p-b -1 and 0.06 ± 0.02 nmol Pyr μmol -1 Lys p-b -1 . It was particularly noticeable, however, that mild heat treatment of raw milk, i.e. pasteurization and UHT treatment, did not significantly increase the amount of both free and protein-bound Lys modifications. In conclusion, the profiles of free and protein-bound glycation-induced Lys modifications were found to be different and a screening of free glycation adducts does, therefore, not allow for a conclusion about the protein glycation status of dairy products

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

Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal.

Science.gov (United States)

Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James

2014-12-01

Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided.

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.

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.

Evidence against the involvement of ionically bound cell wall proteins in pea epicotyl growth

Science.gov (United States)

Melan, M. A.; Cosgrove, D. J.

1988-01-01

Ionically bound cell wall proteins were extracted from 7 day old etiolated pea (Pisum sativum L. cv Alaska) epicotyls with 3 molar LiCl. Polyclonal antiserum was raised in rabbits against the cell wall proteins. Growth assays showed that treatment of growing region segments (5-7 millimeters) of peas with either dialyzed serum, serum globulin fraction, affinity purified immunoglobulin, or papain-cleaved antibody fragments had no effect on growth. Immunofluorescence microscopy confirmed antibody binding to cell walls and penetration of the antibodies into the tissues. Western blot analysis, immunoassay results, and affinity chromatography utilizing Sepharose-bound antibodies confirmed recognition of the protein preparation by the antibodies. Experiments employing in vitro extension as a screening measure indicated no effect upon extension by antibodies, by 50 millimolar LiCl perfusion of the apoplast or by 3 molar LiCl extraction. Addition of cell wall protein to protease pretreated segments did not restore extension nor did addition of cell wall protein to untreated segments increase extension. It is concluded that, although evidence suggests that protein is responsible for the process of extension, the class(es) of proteins which are extracted from pea cell walls with 3 molar LiCl are probably not involved in this process.

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

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,

Proteomic Analysis to Identify Tightly-Bound Cell Wall Protein in Rice Calli

OpenAIRE

Cho, Won Kyong; Hyun, Tae Kyung; Kumar, Dhinesh; Rim, Yeonggil; Chen, Xiong Yan; Jo, Yeonhwa; Kim, Suwha; Lee, Keun Woo; Park, Zee-Yong; Lucas, William J.; Kim, Jae-Yean

2015-01-01

Rice is a model plant widely used for basic and applied research programs. Plant cell wall proteins play key roles in a broad range of biological processes. However, presently, knowledge on the rice cell wall proteome is rudimentary in nature. In the present study, the tightly-bound cell wall proteome of rice callus cultured cells using sequential extraction protocols was developed using mass spectrometry and bioinformatics methods, leading to the identification of 1568 candidate proteins. Ba...

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...

Free and Protein-Bound Maillard Reaction Products in Beer: Method Development and a Survey of Different Beer Types.

Science.gov (United States)

Hellwig, Michael; Witte, Sophia; Henle, Thomas

2016-09-28

The Maillard reaction is important for beer color and flavor, but little is known about the occurrence of individual glycated amino acids in beer. Therefore, seven Maillard reaction products (MRPs), namely, fructosyllysine, maltulosyllysine, pyrraline, formyline, maltosine, MG-H1, and argpyrimidine, were synthesized and quantitated in different types of beer (Pilsner, dark, bock, wheat, and nonalcoholic beers) by HPLC-ESI-MS/MS in the multiple reaction monitoring mode through application of the standard addition method. Free MRPs were analyzed directly. A high molecular weight fraction was isolated by dialysis and hydrolyzed enzymatically prior to analysis. Maltulosyllysine was quantitated for the first time in food. The most important free MRPs in beer are fructosyllysine (6.8-27.0 mg/L) and maltulosyllysine (3.7-21.8 mg/L). Beer contains comparatively high amounts of late-stage free MRPs such as pyrraline (0.2-1.6 mg/L) and MG-H1 (0.3-2.5 mg/L). Minor amounts of formyline (4-230 μg/L), maltosine (6-56 μg/L), and argpyrimidine (0.1-4.1 μg/L) were quantitated. Maltulosyllysine was the most significant protein-bound MRP, but both maltulosyllysine and fructosyllysine represent only 15-60% of the total protein-bound lysine-derived Amadori products. Differences in the patterns of protein-bound and free individual MRPs and the ratios between them were identified, which indicate differences in their chemical, biochemical, and microbiological stabilities during the brewing process.

Utilization of crystalline and protein-bound amino acids by growing-finishing pigs

DEFF Research Database (Denmark)

Nørgaard, Jan Værum; Buxant, L.; Clausen, D.

2016-01-01

It was hypothesized that diets containing crystalline AA (CAA) and protein-bound AA had a comparable nitrogen retention rate, even though the CAA-based diet is optimized as having a standardized ileal digestibility (SID) of 100% for the CAA. Two isoenergetic diets were formulated to provide ident...

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

Backbone resonance assignments for G protein α(i3) subunit in the GDP-bound state.

Science.gov (United States)

Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

2014-10-01

Guanine-nucleotide binding proteins (G proteins) serve as molecular switches in signaling pathways, by coupling the activation of G protein-coupled receptors (GPCRs) at the cell surface to intracellular responses. In the resting state, G protein forms a heterotrimer, consisting of the G protein α subunit with GDP (Gα·GDP) and the G protein βγ subunit (Gβγ). Ligand binding to GPCRs promotes the GDP-GTP exchange on Gα, leading to the dissociation of the GTP-bound form of Gα (Gα·GTP) and Gβγ. Then, Gα·GTP and Gβγ bind to their downstream effector enzymes or ion channels and regulate their activities, leading to a variety of cellular responses. Finally, Gα hydrolyzes the bound GTP to GDP and returns to the resting state by re-associating with Gβγ. The G proteins are classified with four major families based on the amino acid sequences of Gα: i/o, s, q/11, and 12/13. Here, we established the backbone resonance assignments of human Gαi3, a member of the i/o family with a molecular weight of 41 K, in complex with GDP. The chemical shifts were compared with those of Gα(i3) in complex with a GTP-analogue, GTPγS, which we recently reported, indicating that the residues with significant chemical shift differences are mostly consistent with the regions with the structural differences between the GDP- and GTPγS-bound states, as indicated in the crystal structures. The assignments of Gα(i3)·GDP would be useful for the analyses of the dynamics of Gα(i3) and its interactions with various target molecules.

Using isoelectric focussing and neutron activation analysis to study protein-bound tracer elements

International Nuclear Information System (INIS)

Schmelzer, W.

1976-01-01

A method to determine protein-bound tracer elements was determined by combining a protein separation method with neutron activation analysis. Gel filtration, disk electrophoresis, and isoelectric focussing were studied with regard to their suitability as separation methods. Using isoelectric focussing, human serum protein could be separated with good resolution on a preparative scale. The Se, Cr, Ag, Sc, Fe, Zn, Co, Br, Na, Rb, and Cs contents of the various protein fractions were determined by instrumental neutron activation analysis and by gamma-spectroscopic identification of their long-lived nuclides. Particular attention was paid to the main source of error with this method, i.e. contamination of the proteins in the course of the separation process. Information on the binding of the elements to protein was obtained by comparing the contents in the serum and in the protein separated by gel chromatography. For example, 75% of the Se and 30% of the Cs are bound to protein. Contamination of the protein fractions was studied by means of tracer elements with the element Se, errors due to contamination could be ruled out. The method was modified for the special imvestigation of Se-protein complexes in the serum. The Se content was determined by activation analysis via the short-lived radionuclide sup(77m)Se, this considerably reducing the duration of analysis. With regard to focussing, discrimination was improved in the pH region in which specific Se complexes were found. The activity distribution in fractionated serum protein labelled in vitro with 75 Se in the presence of erythrocytes showed that specific labelling is possible in this way. It is thus possible to study the distribution of Se carrier proteins with the aid of a radiotracer technique. (orig./RB) [de

Structure of Rotavirus Outer-Layer Protein VP7 Bound with a Neutralizing Fab

Energy Technology Data Exchange (ETDEWEB)

Aoki, Scott T.; Settembre, Ethan C.; Trask, Shane D.; Greenberg, Harry B.; Harrison, Stephen C.; Dormitzer, Philip R.; (Stanford-MED); (CH-Boston)

2009-06-17

Rotavirus outer-layer protein VP7 is a principal target of protective antibodies. Removal of free calcium ions (Ca{sup 2+}) dissociates VP7 trimers into monomers, releasing VP7 from the virion, and initiates penetration-inducing conformational changes in the other outer-layer protein, VP4. We report the crystal structure at 3.4 angstrom resolution of VP7 bound with the Fab fragment of a neutralizing monoclonal antibody. The Fab binds across the outer surface of the intersubunit contact, which contains two Ca{sup 2+} sites. Mutations that escape neutralization by other antibodies suggest that the same region bears the epitopes of most neutralizing antibodies. The monovalent Fab is sufficient to neutralize infectivity. We propose that neutralizing antibodies against VP7 act by stabilizing the trimer, thereby inhibiting the uncoating trigger for VP4 rearrangement. A disulfide-linked trimer is a potential subunit immunogen.

A Physiologically Based Pharmacokinetic Model to Predict the Pharmacokinetics of Highly Protein-Bound Drugs and Impact of Errors in Plasma Protein Binding

Science.gov (United States)

Ye, Min; Nagar, Swati; Korzekwa, Ken

2015-01-01

Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data was often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding, and blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for terminal elimination half-life (t1/2, 100% of drugs), peak plasma concentration (Cmax, 100%), area under the plasma concentration-time curve (AUC0–t, 95.4%), clearance (CLh, 95.4%), mean retention time (MRT, 95.4%), and steady state volume (Vss, 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. PMID:26531057

A method for analysing small samples of floral pollen for free and protein-bound amino acids.

Science.gov (United States)

Stabler, Daniel; Power, Eileen F; Borland, Anne M; Barnes, Jeremy D; Wright, Geraldine A

2018-02-01

Pollen provides floral visitors with essential nutrients including proteins, lipids, vitamins and minerals. As an important nutrient resource for pollinators, including honeybees and bumblebees, pollen quality is of growing interest in assessing available nutrition to foraging bees. To date, quantifying the protein-bound amino acids in pollen has been difficult and methods rely on large amounts of pollen, typically more than 1 g. More usual is to estimate a crude protein value based on the nitrogen content of pollen, however, such methods provide no information on the distribution of essential and non-essential amino acids constituting the proteins.Here, we describe a method of microwave-assisted acid hydrolysis using low amounts of pollen that allows exploration of amino acid composition, quantified using ultra high performance liquid chromatography (UHPLC), and a back calculation to estimate the crude protein content of pollen.Reliable analysis of protein-bound and free amino acids as well as an estimation of crude protein concentration was obtained from pollen samples as low as 1 mg. Greater variation in both protein-bound and free amino acids was found in pollen sample sizes amino acids in smaller sample sizes, we suggest a correction factor to apply to specific sample sizes of pollen in order to estimate total crude protein content.The method described in this paper will allow researchers to explore the composition of amino acids in pollen and will aid research assessing the available nutrition to pollinating animals. This method will be particularly useful in assaying the pollen of wild plants, from which it is difficult to obtain large sample weights.

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....

Protein-bound NAD(P)H Lifetime is Sensitive to Multiple Fates of Glucose Carbon.

Science.gov (United States)

Sharick, Joe T; Favreau, Peter F; Gillette, Amani A; Sdao, Sophia M; Merrins, Matthew J; Skala, Melissa C

2018-04-03

While NAD(P)H fluorescence lifetime imaging (FLIM) can detect changes in flux through the TCA cycle and electron transport chain (ETC), it remains unclear whether NAD(P)H FLIM is sensitive to other potential fates of glucose. Glucose carbon can be diverted from mitochondria by the pentose phosphate pathway (via glucose 6-phosphate dehydrogenase, G6PDH), lactate production (via lactate dehydrogenase, LDH), and rejection of carbon from the TCA cycle (via pyruvate dehydrogenase kinase, PDK), all of which can be upregulated in cancer cells. Here, we demonstrate that multiphoton NAD(P)H FLIM can be used to quantify the relative concentrations of recombinant LDH and malate dehydrogenase (MDH) in solution. In multiple epithelial cell lines, NAD(P)H FLIM was also sensitive to inhibition of LDH and PDK, as well as the directionality of LDH in cells forced to use pyruvate versus lactate as fuel sources. Among the parameters measurable by FLIM, only the lifetime of protein-bound NAD(P)H (τ 2 ) was sensitive to these changes, in contrast to the optical redox ratio, mean NAD(P)H lifetime, free NAD(P)H lifetime, or the relative amount of free and protein-bound NAD(P)H. NAD(P)H τ 2 offers the ability to non-invasively quantify diversions of carbon away from the TCA cycle/ETC, which may support mechanisms of drug resistance.

Comparative LC-MS/MS profiling of free and protein-bound early and advanced glycation-induced lysine modifications in dairy products

Energy Technology Data Exchange (ETDEWEB)

Hegele, Joerg [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)], E-mail: joerg.hegele@rdls.nestle.com; Buetler, Timo; Delatour, Thierry [Nestle Research Centre, Nestec Ltd., Vers-chez-les-Blanc, CH-1000 Lausanne 26 (Switzerland)

2008-06-09

Free and protein-bound forms of early and advanced glycation-induced lysine (Lys) modifications were quantified in dairy products by LC-MS/MS using a stable isotope dilution assay. The glycation profiles for N{sup {epsilon}}-fructoselysine (FL), N{sup {epsilon}}-carboxymethyllysine (CML) and pyrraline (Pyr) were monitored in raw and processed cow milk to investigate whether free glycation products could serve as fast and simple markers to assess the extent of protein glycation in dairy products. In all milk samples, the fraction of free glycation adducts was predominantly composed of advanced modifications, e.g. 8.34 {+-} 3.81 nmol CML per {mu}mol of free Lys (Lys{sub free}) and 81.5 {+-} 87.8 nmol Pyr {mu}mol{sup -1} Lys{sub free}{sup -1} vs. 3.72 {+-} 1.29 nmol FL {mu}mol{sup -1} Lys{sub free}{sup -1}. In contrast, the protein-bound early glycation product FL considerably outweighed the content of CML and Pyr in milk proteins of raw and processed cow milk, whereas severely heat treated milk products, e.g. condensed milk, contained a higher amount of protein-bound advanced glycation adducts. Typical values recorded for milk samples processed under mild conditions were 0.47 {+-} 0.08 nmol FL {mu}mol{sup -1} of protein-bound Lys (Lys{sub p-b}), 0.04 {+-} 0.03 nmol CML {mu}mol{sup -1} Lys{sub p-b}{sup -1} and 0.06 {+-} 0.02 nmol Pyr {mu}mol{sup -1} Lys{sub p-b}{sup -1}. It was particularly noticeable, however, that mild heat treatment of raw milk, i.e. pasteurization and UHT treatment, did not significantly increase the amount of both free and protein-bound Lys modifications. In conclusion, the profiles of free and protein-bound glycation-induced Lys modifications were found to be different and a screening of free glycation adducts does, therefore, not allow for a conclusion about the protein glycation status of dairy products.

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.

Dynamic features of apo and bound HIV-Nef protein reveal the anti-HIV dimerization inhibition mechanism.

Science.gov (United States)

Moonsamy, Suri; Bhakat, Soumendranath; Soliman, Mahmoud E S

2015-01-01

The first account on the dynamic features of Nef or negative factor, a small myristoylated protein located in the cytoplasm believes to increase HIV-1 viral titer level, is reported herein. Due to its major role in HIV-1 pathogenicity, Nef protein is considered an emerging target in anti-HIV drug design and discovery process. In this study, comparative long-range all-atom molecular dynamics simulations were employed for apo and bound protein to unveil molecular mechanism of HIV-Nef dimerization and inhibition. Results clearly revealed that B9, a newly discovered Nef inhibitor, binds at the dimeric interface of Nef protein and caused significant separation between orthogonally opposed residues, namely Asp108, Leu112 and Gln104. Large differences in magnitudes were observed in the radius of gyration (∼1.5 Å), per-residue fluctuation (∼2 Å), C-alpha deviations (∼2 Å) which confirm a comparatively more flexible nature of apo conformation due to rapid dimeric association. Compared to the bound conformer, a more globally correlated motion in case of apo structure of HIV-Nef confirms the process of dimeric association. This clearly highlights the process of inhibition as a result of ligand binding. The difference in principal component analysis (PCA) scatter plot and per-residue mobility plot across first two normal modes further justifies the same findings. The in-depth dynamic analyses of Nef protein presented in this report would serve crucial in understanding its function and inhibition mechanisms. Information on inhibitor binding mode would also assist in designing of potential inhibitors against this important HIV target.

A Review on Structures and Functions of Bcl-2 Family Proteins from Homo sapiens.

Science.gov (United States)

Sivakumar, Dakshinamurthy; Sivaraman, Thirunavukkarasu

2016-01-01

Cancer cells evade apoptosis, which is regulated by proteins of Bcl-2 family in the intrinsic pathways. Numerous experimental three-dimensional (3D) structures of the apoptotic proteins and the proteins bound with small chemical molecules/peptides/proteins have been reported in the literature. In this review article, the 3D structures of the Bcl-2 family proteins from Homo sapiens and as well complex structures of the anti-apoptotic proteins bound with small molecular inhibitors reported in the literature to date have been comprehensively listed out and described in detail. Moreover, the molecular mechanisms by which the Bcl-2 family proteins modulate the apoptotic processes and strategies for designing antagonists to anti-apoptotic proteins have been concisely discussed.

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

Role of protein-bound carbonyl groups in the formation of advanced glycation endproducts.

Science.gov (United States)

Liggins, J; Furth, A J

1997-08-22

Several mechanisms have been postulated for the formation of advanced glycation endproducts (AGEs) from glycated proteins; they all feature protein-bound carbonyl intermediates. Using 2,4-dinitrophenylhydrazine (DNPH), we have detected these intermediates on bovine serum albumin, lysozyme and beta-lactoglobulin after in vitro glycation by glucose or fructose. Carbonyls were formed in parallel with AGE-fluorophores, via oxidative Maillard reactions. Neither Amadori nor Heyns products contributed to the DNPH reaction. Fluorophore and carbonyl yields were much enhanced in lipid-associated proteins, but both groups could also be detected in lipid-free proteins. When pre-glycated proteins were incubated in the absence of free sugar, carbonyl groups were rapidly lost in a first-order reaction, while fluorescence continued to develop beyond the 21 days of incubation. Another unexpected finding was that not all carbonyl groups were blocked by aminoguanidine, although there was complete inhibition of reactions leading to AGE-fluorescence. It is suggested that carbonyls acting as fluorophore precursors react readily with aminoguanidine, while others are resistant to this hydrazine, possibly because they are involved in ring closure. Factors influencing the relative rates of acyclisation and hydrazone formation are discussed, together with possible implications for antiglycation therapy.

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.

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

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.

Comparison of methods for determination of testosterone and non-protein bound testosterone in men with alcoholic liver disease

DEFF Research Database (Denmark)

Gluud, C; Bennett, Patrick

1986-01-01

The serum concentrations of testosterone and of non-protein bound testosterone were determined in 28 men with alcoholic liver disease having normal to decreased serum albumin concentrations and normal to raised SHBG concentrations. Serum testosterone concentrations determined with two...... radioimmunoassays using different purification procedures and antibody batches did not differ significantly and correlated significantly (r=0.91; p less than 0.001). The median serum concentration of non-protein bound testosterone was 0.265 nmol/l (range 0.068-0.495 nmol/l) when determined by equilibrium dialysis...... and 0.232 nmol/l (range 0.042-0.610 nmol/l) when calculated according to the law of mass action. This difference is insignificant. The concentrations of non-protein bound testosterone determined by the two methods correlated significantly (r=0.83; p less than 0.001). In the calculation of non...

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,

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.

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

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

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.

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.

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.

PLD2 has both enzymatic and cell proliferation-inducing capabilities, that are differentially regulated by phosphorylation and dephosphorylation

International Nuclear Information System (INIS)

Henkels, Karen M.; Short, Stephen; Peng, Hong-Juan; Fulvio, Mauricio Di; Gomez-Cambronero, Julian

2009-01-01

Phospholipase D2 (PLD2) overexpression in mammalian cells results in cell transformation. We have hypothesized that this is due to an increase of de novo DNA synthesis. We show here that overexpression of PLD2-WT leads to an increased DNA synthesis, as measured by the expression levels of the proliferation markers PCNA, p27 KIP1 and phospho-histone-3. The enhancing effect was even higher with phosphorylation-deficient PLD2-Y179F and PLD2-Y511F mutants. The mechanism for this did not involve the enzymatic activity of the lipase, but, rather, the presence of the protein tyrosine phosphatase CD45, as silencing with siRNA for CD45 abrogated the effect. The two Y→F mutants had in common a YxN consensus site that, in the phosphorylated counterparts, could be recognized by SH2-bearing proteins, such as Grb2. Even though Y179F and Y511F cannot bind Grb2, they could still find other protein partners, one of which, we have reasoned, could be CD45 itself. Affinity purified PLD2 is indeed activated by Grb2 and deactivated by CD45 in vitro. We concluded that phosphorylated PLD2, aided by Grb2, mediates lipase activity, whereas dephosphorylated PLD2 mediates an induction of cell proliferation, and the specific residues involved in this newly discovered regulation of PLD2 are Y 179 and Y 511 .

Interconversion of two GDP-bound conformations and their selection in an Arf-family small G protein.

Science.gov (United States)

Okamura, Hideyasu; Nishikiori, Masaki; Xiang, Hongyu; Ishikawa, Masayuki; Katoh, Etsuko

2011-07-13

ADP-ribosylation factor (Arf) and other Arf-family small G proteins participate in many cellular functions via their characteristic GTP/GDP conformational cycles, during which a nucleotide(∗)Mg(2+)-binding site communicates with a remote N-terminal helix. However, the conformational interplay between the nucleotides, the helix, the protein core, and Mg(2+) has not been fully delineated. Herein, we report a study of the dynamics of an Arf-family protein, Arl8, under various conditions by means of NMR relaxation spectroscopy. The data indicated that, when GDP is bound, the protein core, which does not include the N-terminal helix, reversibly transition between an Arf-family GDP form and another conformation that resembles the Arf-family GTP form. Additionally, we found that the N-terminal helix and Mg(2+), respectively, stabilize the aforementioned former and latter conformations in a population-shift manner. Given the dynamics of the conformational changes, we can describe the Arl8 GTP/GDP cycle in terms of an energy diagram. Copyright © 2011 Elsevier Ltd. All rights reserved.

Crystal Structures of SlyA Protein, a Master Virulence Regulator of Salmonella, in Free and DNA-bound States

Energy Technology Data Exchange (ETDEWEB)

Dolan, Kyle T.; Duguid, Erica M.; He, Chuan (UC)

2011-11-17

SlyA is a master virulence regulator that controls the transcription of numerous genes in Salmonella enterica. We present here crystal structures of SlyA by itself and bound to a high-affinity DNA operator sequence in the slyA gene. SlyA interacts with DNA through direct recognition of a guanine base by Arg-65, as well as interactions between conserved Arg-86 and the minor groove and a large network of non-base-specific contacts with the sugar phosphate backbone. Our structures, together with an unpublished structure of SlyA bound to the small molecule effector salicylate (Protein Data Bank code 3DEU), reveal that, unlike many other MarR family proteins, SlyA dissociates from DNA without large conformational changes when bound to this effector. We propose that SlyA and other MarR global regulators rely more on indirect readout of DNA sequence to exert control over many genes, in contrast to proteins (such as OhrR) that recognize a single operator.

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.

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.

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.

Protein-bound solute removal during extended multipass versus standard hemodialysis

DEFF Research Database (Denmark)

Eloot, Sunny; Van Biesen, Wim; Axelsen, Mette

2015-01-01

and middle molecules compared to standard hemodialysis (SHD). Since protein-bound solutes (PBS) exert important pathophysiological effects, we investigated whether MPHD results in improved removal of PBS as well. METHODS: A cross-over study (Clinical Trial NCT01267760) was performed in nine stable HD......), hippuric acid (HA), indole acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (PCS). Dialyser extraction ratio, reduction ratio, and solute removal were calculated for these solutes. RESULTS: Already at 60 min after dialysis start, the extraction ratio in the hemodialyser was a factor 1.4-4 lower...

A physiologically based pharmacokinetic model to predict the pharmacokinetics of highly protein-bound drugs and the impact of errors in plasma protein binding.

Science.gov (United States)

Ye, Min; Nagar, Swati; Korzekwa, Ken

2016-04-01

Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data were often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding and the blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate the model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for the terminal elimination half-life (t1/2 , 100% of drugs), peak plasma concentration (Cmax , 100%), area under the plasma concentration-time curve (AUC0-t , 95.4%), clearance (CLh , 95.4%), mean residence time (MRT, 95.4%) and steady state volume (Vss , 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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...

Differential Effects of Camel Milk on Insulin Receptor Signaling – Towards Understanding the Insulin-like Properties of Camel Milk

Directory of Open Access Journals (Sweden)

Abdulrasheed O Abdulrahman

2016-01-01

Full Text Available Previous studies on the Arabian camel (Camelus dromedarius showed beneficial effects of its milk reported in diverse models of human diseases including a substantial hypoglycemic activity. However, the cellular and molecular mechanisms involved in such effects remain completely unknown. In this study, we hypothesized that camel milk may act at the level of human insulin receptor (hIR and its related intracellular signaling pathways. Therefore, we examined the effect of camel milk on the activation of hIR transiently expressed in human embryonic kidney 293 (HEK293 cells using bioluminescence resonance energy transfer (BRET technology. BRET was used to assess, in live cells and real-time, the physical interaction between hIR and insulin receptor signaling proteins (IRS1 and the growth factor receptor-bound protein 2 (Grb2. Our data showed that camel milk did not promote any increase in the BRET signal between hIR and IRS1 or Grb2 in the absence of insulin stimulation. However, it significantly potentiated the maximal insulin-promoted BRET signal between hIR and Grb2 but not IRS1. Interestingly, camel milk appears to differentially impact the downstream signaling since it significantly activated ERK1/2 and potentiated the insulin-induced ERK1/2 but not Akt activation. These observations are to some extent consistent with the BRET data since ERK1/2 and Akt activation are known to reflect the engagement of Grb2 and IRS1 pathways, respectively. The preliminary fractionation of camel milk suggests the peptide/protein nature of the active component in camel milk. Together, our study demonstrates for the first time an allosteric effect of camel milk on insulin receptor conformation and activation with differential effects on its intracellular signaling. These findings should help to shed more light on the hypoglycemic activity of camel milk with potential therapeutic applications.

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.

Structure of a rare non-standard sequence k-turn bound by L7Ae protein

Science.gov (United States)

Huang, Lin; Lilley, David M.J.

2014-01-01

Kt-23 from Thelohania solenopsae is a rare RNA kink turn (k-turn) where an adenine replaces the normal guanine at the 2n position. L7Ae is a member of a strongly conserved family of proteins that bind a range of k-turn structures in the ribosome, box C/D and H/ACA small nucleolar RNAs and U4 small nuclear RNA. We have solved the crystal structure of T. solenopsae Kt-23 RNA bound to Archeoglobus fulgidus L7Ae protein at a resolution of 2.95 Å. The protein binds in the major groove displayed on the outer face of the k-turn, in a manner similar to complexes with standard k-turn structures. The k-turn adopts a standard N3 class conformation, with a single hydrogen bond from A2b N6 to A2n N3. This contrasts with the structure of the same sequence located in the SAM-I riboswitch, where it adopts an N1 structure, showing the inherent plasticity of k-turn structure. This potentially can affect any tertiary interactions in which the RNA participates. PMID:24482444

Competition between bound and free peptides in an ELISA-based procedure that assays peptides derived from protein digests

Directory of Open Access Journals (Sweden)

Pace Umberto

2006-05-01

Full Text Available Abstract Background We describe an ELISA-based method that can be used to identify and quantitate proteins in biological samples. In this method, peptides in solution, derived from proteolytic digests of the sample, compete with substrate-attached synthetic peptides for antibodies, also in solution, generated against the chosen peptides. The peptides used for the ELISA are chosen on the basis of their being (i products of the proteolytic (e.g. tryptic digestion of the protein to be identified and (ii unique to the target protein, as far as one can know from the published sequences. Results In this paper we describe the competition assay and we define the optimal conditions for the most effective assay. We have performed an analysis of the kinetics of interaction between the four components of the assay: the plastic substratum to which the peptide is bound, the bound peptide itself, the competing added peptide, and the antibody that is specific for the peptide and we compare the results of theoretical simulations to the actual data in some model systems. Conclusion The data suggest that the peptides bind to the plastic substratum in more than one conformation and that, once bound, the peptide displays different affinities for the antibody, depending on how it has bound to the plate

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

Binding of monoclonal antibody to protein antigen in fluid phase or bound to solid supports

Energy Technology Data Exchange (ETDEWEB)

Kennel, S J

1982-01-01

Rat monoclonal antibody (MoAb) to fragment D (FgD) of human fibrinogen was used to characterize the direct binding of antibody to protein in solution or bound to solid supports. Purified IgG, F(ab')/sub 2/ and Fab' were prepared from ascites fluid of hybridoma 104-14B which is a fusion product of spleen cells from a rat immunized with FgD and the mouse myeloma cell line, P3-X63-Ag8. Two-dimensional electrophoresis of radioiodinated antibody preparations demonstrated the presence of hybrid immunoglobulin molecules, but only structures having rat heavy and rat light chains had active antibody combinig sites. The affinity constant for IgG as well as F(ab')/sub 2/ and Fab', 6x10/sup 9/ M/sup -1/, was identical when tested using fluid phase antigen (/sup 125/I-labeled FgD). Affinity constants determined for direct binding of iodinated IgG using FgD immobilized on solid supports showed a slight dependence on the antigen concentration used in the measurement. These values ranged from 0.5x10/sup 9/ M/sup -1/ at high antigen concentrations (1.3x10/sup -7/ M) to 9x10/sup 9/ M/sup -1/ at low antigen concentration (1.3x10/sup -10/ M). Binding constants for F(ab')/sub 2/ and Fab' gave similar results indicating that binding was homogeneous and univalent. The capacity of solid state antigen to bind antibody varied with the method used to bind FgD to the solid support. FgD bound directly to polystyrene plates was least efficient at binding labeled antibody; FgD bound to plates through intermediate carriers poly(L-lysine) was only slightly more efficient, while antigen bound to Sepharose beads by cyanogen bromide activation was the most active.

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...

Inhibitory profiles of spices against free and protein-bound heterocyclic amines of roast beef patties as revealed by ultra-performance liquid chromatography-tandem mass spectrometry and principal component analysis.

Science.gov (United States)

Chen, Jing; He, Zhiyong; Qin, Fang; Chen, Jie; Cao, Dongsheng; Guo, Fengxian; Zeng, Maomao

2017-11-15

The effects of various levels of chili pepper, Sichuan pepper, and black pepper on the amounts of 17 heterocyclic amines (HAs) from seven categories of both free and protein-bound states in roast beef patties were assessed by ultra-performance liquid chromatography-tandem mass spectrometry combined with principal component analysis. Three groups of HA, including imidazopyridines (DMIP), imidazoquinoxalines (MeIQx and 4,8-MeIQx), and β-carbolines (norharman and harman), were detected and quantified in both their free and protein-bound states, whereas PhIP was detected only in its free state, and imidazoquinolines (IQ, IQ[4,5-b], and MeIQ), α-carbolines (AαC and MeAαC), and phenylpyridines (Phe-P-1) were detected only in their protein-bound states. The results demonstrate that the peppers at all three levels had significant inhibitory effects on free PhIP, DMIP, MeIQx, and 4,8-DiMeIQx and could promote free norharman. Harman was significantly suppressed by chili pepper and black pepper, but enhanced by Sichuan pepper. All 11 protein-bound HAs, with the exception of IQ, IQ[4,5-b], and MeIQx with added chili pepper, were significantly reduced by the three peppers. The total amounts of the free and protein-bound states of all 11 HAs (1692.4 ± 78.9 ng g -1 ), imidazopyridines (5.5 ± 0.2 ng g -1 ), imidazoquinolines (7.2 ± 0.2 ng g -1 ), imidazoquinoxalines (6.9 ± 0.2 ng g -1 ), α-carbolines (20.1 ± 0.4 ng g -1 ), and β-carbolines (1651.7 ± 79.5 ng g -1 ) were suppressed by each level of all of the three peppers except for 0.5% and 1.0% chili pepper. Our findings may facilitate the inhibition of HA formation in the processing of meat products.

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....

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

Crystal structure of axolotl (Ambystoma mexicanum) liver bile acid-binding protein bound to cholic and oleic acid.

Science.gov (United States)

Capaldi, Stefano; Guariento, Mara; Perduca, Massimiliano; Di Pietro, Santiago M; Santomé, José A; Monaco, Hugo L

2006-07-01

The family of the liver bile acid-binding proteins (L-BABPs), formerly called liver basic fatty acid-binding proteins (Lb-FABPs) shares fold and sequence similarity with the paralogous liver fatty acid-binding proteins (L-FABPs) but has a different stoichiometry and specificity of ligand binding. This article describes the first X-ray structure of a member of the L-BABP family, axolotl (Ambystoma mexicanum) L-BABP, bound to two different ligands: cholic and oleic acid. The protein binds one molecule of oleic acid in a position that is significantly different from that of either of the two molecules that bind to rat liver FABP. The stoichiometry of binding of cholate is of two ligands per protein molecule, as observed in chicken L-BABP. The cholate molecule that binds buried most deeply into the internal cavity overlaps well with the analogous bound to chicken L-BABP, whereas the second molecule, which interacts with the first only through hydrophobic contacts, is more external and exposed to the solvent. (c) 2006 Wiley-Liss, Inc.

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.

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.

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.

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

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.

Crystal Structures of Apo and Metal-Bound Forms of the UreE Protein from Helicobacter pylori: Role of Multiple Metal Binding Sites

Energy Technology Data Exchange (ETDEWEB)

Shi, Rong; Munger, Christine; Asinas, Abdalin; Benoit, Stephane L.; Miller, Erica; Matte, Allan; Maier, Robert J.; Cygler, Miroslaw (McGill); (Georgia); (Biotech Res.)

2010-10-22

The crystal structure of the urease maturation protein UreE from Helicobacter pylori has been determined in its apo form at 2.1 {angstrom} resolution, bound to Cu{sup 2+} at 2.7 {angstrom} resolution, and bound to Ni{sup 2+} at 3.1 {angstrom} resolution. Apo UreE forms dimers, while the metal-bound enzymes are arranged as tetramers that consist of a dimer of dimers associated around the metal ion through coordination by His102 residues from each subunit of the tetramer. Comparison of independent subunits from different crystal forms indicates changes in the relative arrangement of the N- and C-terminal domains in response to metal binding. The improved ability of engineered versions of UreE containing hexahistidine sequences at either the N-terminal or C-terminal end to provide Ni{sup 2+} for the final metal sink (urease) is eliminated in the H102A version. Therefore, the ability of the improved Ni{sup 2+}-binding versions to deliver more nickel is likely an effect of an increased local concentration of metal ions that can rapidly replenish transferred ions bound to His102.

An NMR strategy for fragment-based ligand screening utilizing a paramagnetic lanthanide probe

International Nuclear Information System (INIS)

Saio, Tomohide; Ogura, Kenji; Shimizu, Kazumi; Yokochi, Masashi; Burke, Terrence R.; Inagaki, Fuyuhiko

2011-01-01

A nuclear magnetic resonance-based ligand screening strategy utilizing a paramagnetic lanthanide probe is presented. By fixing a paramagnetic lanthanide ion to a target protein, a pseudo-contact shift (PCS) and a paramagnetic relaxation enhancement (PRE) can be observed for both the target protein and its bound ligand. Based on PRE and PCS information, the bound ligand is then screened from the compound library and the structure of the ligand–protein complex is determined. PRE is an isotropic paramagnetic effect observed within 30 Å from the lanthanide ion, and is utilized for the ligand screening in the present study. PCS is an anisotropic paramagnetic effect providing long-range (∼40 Å) distance and angular information on the observed nuclei relative to the paramagnetic lanthanide ion, and utilized for the structure determination of the ligand–protein complex. Since a two-point anchored lanthanide-binding peptide tag is utilized for fixing the lanthanide ion to the target protein, this screening method can be generally applied to non-metal-binding proteins. The usefulness of this strategy was demonstrated in the case of the growth factor receptor-bound protein 2 (Grb2) Src homology 2 (SH2) domain and its low- and high-affinity ligands.

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...

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

A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

Science.gov (United States)

Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

2016-02-01

Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

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.

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.

Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2)

International Nuclear Information System (INIS)

Marr, Eric; Tardie, Mark; Carty, Maynard; Brown Phillips, Tracy; Wang, Ing-Kae; Soeller, Walt; Qiu, Xiayang; Karam, George

2006-01-01

The crystal structure of human adipocyte lipid-binding protein (aP2) with a bound palmitate is reported at 1.5 Å resolution. Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5 Å resolution. Unlike the known crystal structure of murine aP2 in complex with palmitate, this structure shows that the fatty acid is in a folded conformation and that the loop containing Phe57 acts as a lid to regulate ligand binding by excluding solvent exposure to the central binding cavity

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...

N=2 central charge bounds from 2d chiral algebras

Energy Technology Data Exchange (ETDEWEB)

Lemos, Madalena [DESY Hamburg, Theory Group,Notkestrasse 85, D-22607 Hamburg (Germany); Liendo, Pedro [IMIP, Humboldt-Universität zu Berlin, IRIS Adlershof,Zum Großen Windkanal 6, 12489 Berlin (Germany)

2016-04-01

We study protected correlation functions in N=2 SCFT whose description is captured by a two-dimensional chiral algebra. Our analysis implies a new analytic bound for the c-anomaly as a function of the flavor central charge k, valid for any theory with a flavor symmetry. Combining our result with older bounds in the literature puts strong constraints on the parameter space of N=2 theories. In particular, it singles out a special set of models whose value of c is uniquely fixed once k is given. This set includes the canonical rank one N=2 SCFTs given by Kodaira’s classification.

Pressurized liquid extraction-assisted mussel cytosol preparation for the determination of metals bound to metallothionein-like proteins

International Nuclear Information System (INIS)

Santiago-Rivas, Sandra; Moreda-Pineiro, Antonio; Bermejo-Barrera, Pilar; Moreda-Pineiro, Jorge; Alonso-Rodriguez, Elia; Muniategui-Lorenzo, Soledad; Lopez-Mahia, Purificacion; Prada-Rodriguez, Dario

2007-01-01

The possibilities of pressurized liquid extraction (PLE) have been novelty tested to assist the cytosol preparation from wet mussel soft tissue before the determination of metals bound to metallothionein-like proteins (MLPs). Results obtained after PLE were compared with those obtained after a classical blending procedure for mussel cytosolic preparation. Isoforms MLP-1 (retention time of 4.1 min) and MLP-2 (retention time of 7.4 min) were separated by anion exchange high-performance liquid chromatography (HPLC) and the concentrations of Ba, Cu, Mn, Sr and Zn bound to MLP isoforms were directly measured by inductively coupled plasma-atomic emission spectrometry (ICP-OES) as a multi-element detector. The optimized PLE-assisted mussel cytosol preparation has consisted of one extraction cycle at room temperature and 1500 psi for 2 min. Since separation between the solid mussel residue and the extract (cytosol) is performed by the PLE system, the cytosol preparation method is faster than conventional cytosol preparation methods by cutting/blending using Ultraturrax or Stomacher devices

Crystallization and preliminary X-ray diffraction analysis of phospholipid-bound Sfh1p, a member of the Saccharomyces cerevisiae Sec14p-like phosphatidylinositol transfer protein family

International Nuclear Information System (INIS)

Schaaf, Gabriel; Betts, Laurie; Garrett, Teresa A.; Raetz, Christian R. H.; Bankaitis, Vytas A.

2006-01-01

Yeast Sfh1p, a close homolog of the Sec14p phosphatidylinositol transfer protein, was crystallized in the absence of detergent. X-ray data have been collected to 2.5 Å. Sec14p is the major phosphatidylinositol (PtdIns)/phosphatidylcholine (PtdCho) transfer protein in the budding yeast Saccharomyces cerevisiae and is the founding member of a large eukaryotic protein superfamily. This protein catalyzes the exchange of either PtdIns or PtdCho between membrane bilayers in vitro and this exchange reaction requires no external input of energy or of other protein cofactors. Despite the previous elucidation of the crystal structure of a detergent-bound form of Sec14p, the conformational changes that accompany the phospholipid-exchange reaction remain undefined. Moreover, a structural appreciation of how Sec14p or its homologs bind their various phospholipid substrates remains elusive. Here, the purification and crystallization of yeast Sfh1p, the protein most closely related to Sec14p, are reported. A combination of electrospray ionization mass-spectrometry and collision-induced decomposition mass-spectrometry methods indicate that recombinant Sfh1p loads predominantly with phosphatidylethanolamine. Unlike phospholipid-bound forms of Sec14p, this form of Sfh1p crystallizes readily in the absence of detergent. Sfh1p crystals diffract to 2.5 Å and belong to the orthorhombic primitive space group P2 1 2 1 2 1 , with unit-cell parameters a = 49.40, b = 71.55, c = 98.21 Å, α = β = γ = 90°. One Sfh1p molecule is present in the asymmetric unit (V M = 2.5 Å 3 Da −1 ; V s = 50%). Crystallization of a phospholipid-bound Sec14p-like protein is a critical first step in obtaining the first high-resolution picture of how proteins of the Sec14p superfamily bind their phospholipid ligands. This information will significantly extend our current understanding of how Sec14p-like proteins catalyze phospholipid exchange

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.

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...

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

Analysis of protein-bound metabolites of furazolidone and furaltadone in pig liver by high performance liquid chromatography and liquid chromatography mass spectrometry

NARCIS (Netherlands)

Horne, E.; Cadogan, A.; O'Keeffe, M.; Hoogenboom, L.A.P.

1996-01-01

Studies undertaken using radiolabelled furazolidone have demonstrated the covalent binding of residues of the drug to cellular protein in vivo. A portion of these bound residues and those formed by furaltadone, a related nitrofuran drug, possess intact side-chains, 3-amino-2-oxazolidinone (AOZ) and

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.

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.

Absorption and retention of free and milk protein-bound cyano- and hydroxocobalamins

DEFF Research Database (Denmark)

Kornerup, Linda Skibsted; Juul, Christian Bredgaard; Fedosov, Sergey

2016-01-01

alone or bound to milk protein. Materials and methods We synthesized labeled OH[57Co]Cbl from commercially available CN[57Co]Cbl. Recombinant bovine transcobalamin (rbTC) was produced in yeast and skimmed milk obtained off the shelf. Male Wistar rats (250–300 g) received labeled Cbl by gastric gavage...... and CNCbl are absorbed equally well, but much more OHCbl accumulated in the liver. Benefits of oral supplementation with OHCbl compared to CNCbl should be investigated....

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...

Evidence for the Existence of One Antenna-Associated, Lipid-Dissolved and Two Protein-Bound Pools of Diadinoxanthin Cycle Pigments in Diatoms[C][W

Science.gov (United States)

Lepetit, Bernard; Volke, Daniela; Gilbert, Matthias; Wilhelm, Christian; Goss, Reimund

2010-01-01

We studied the localization of diadinoxanthin cycle pigments in the diatoms Cyclotella meneghiniana and Phaeodactylum tricornutum. Isolation of pigment protein complexes revealed that the majority of high-light-synthesized diadinoxanthin and diatoxanthin is associated with the fucoxanthin chlorophyll protein (FCP) complexes. The characterization of intact cells, thylakoid membranes, and pigment protein complexes by absorption and low-temperature fluorescence spectroscopy showed that the FCPs contain certain amounts of protein-bound diadinoxanthin cycle pigments, which are not significantly different in high-light and low-light cultures. The largest part of high-light-formed diadinoxanthin cycle pigments, however, is not bound to antenna apoproteins but located in a lipid shield around the FCPs, which is copurified with the complexes. This lipid shield is primarily composed of the thylakoid membrane lipid monogalactosyldiacylglycerol. We also show that the photosystem I (PSI) fraction contains a tightly connected FCP complex that is enriched in protein-bound diadinoxanthin cycle pigments. The peripheral FCP and the FCP associated with PSI are composed of different apoproteins. Tandem mass spectrometry analysis revealed that the peripheral FCP is composed mainly of the light-harvesting complex protein Lhcf and also significant amounts of Lhcr. The PSI fraction, on the other hand, shows an enrichment of Lhcr proteins, which are thus responsible for the diadinoxanthin cycle pigment binding. The existence of lipid-dissolved and protein-bound diadinoxanthin cycle pigments in the peripheral antenna and in PSI is discussed with respect to different specific functions of the xanthophylls. PMID:20935178

Free and protein-bound cobalamin absorption in healthy middle-aged and older subjects.

Science.gov (United States)

van Asselt, D Z; van den Broek, W J; Lamers, C B; Corstens, F H; Hoefnagels, W H

1996-08-01

To study free- and protein-bound cobalamin absorption and the correlation with atrophic gastritis in healthy middle-aged and older subjects. A cross-sectional study. Fifty-two healthy subjects, aged 26 to 87 years, apparently free from conditions known to influence the cobalamin status. Middle-aged subjects were defined as those younger than 65 years of age (median age 57 years) and older subjects as those 65 years and older (median age 75 years). Protein-bound cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of scrambled egg yolk, labeled in vivo with 57 Co-cobalamin by injecting a hen with 57 Co-cyanocobalamin. The percentage of 57 Co-cobalamin bound to protein was 65%. Free cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of crystalline 57 Co-cyanocobalamin. Plasma cobalamin, folate and fasting plasma gastrin, and pepsinogen A and C concentrations were determined. The median urinary excretion of egg yolk 57 Co-cobalamin in middle-aged subjects was 12.3% (25th and 75th percentiles 10.5%-14.5%) compared with 11.7% (25th and 75th percentiles 9.8%-13.6%) in older subjects (P = .283). The median urinary excretion after administration of free 57 Co-cobalamin in middle-aged subjects was 25.7% (25th and 75th percentiles 20.6%-30.7%) compared with 27.9% (25th and 75th percentiles 21.4%-34.5%) in older subjects (P = .694). Neither egg yolk nor free 57 Co-cobalamin excretion correlated with age. A ratio of pepsinogen A to pepsinogen C less than 1.6, indicating atrophic gastritis, was found in 13 subjects. Within the atrophic gastritis group, 11 subjects had a pepsinogen A concentration greater than or equal to 17 micrograms/L, indicating mild to moderate atrophic gastritis, and two subjects had a pepsinogen A concentration less than 17 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. All subjects had normal fasting plasma gastrin concentrations. Free

An albumin-fixed membrane for the removal of protein-bound toxins

International Nuclear Information System (INIS)

Ge Dongtao; Wu Dewang; Shi Wei; Ma Yuanyuan; Tian Xiangdong; Liang Pengfei; Zhang Qiqing

2006-01-01

Established methods for kidney dialysis do not work for liver failure because kidney dialysis removes only water-soluble toxins, while the liver normally removes albumin-bound toxins. In the present study, a polysulfone dialysis membrane with a -OH reactive group was prepared by hydrolyzing the chloromethylated polysulfone membrane, and the bovine serum albumin molecules were fixed into the membrane with 1,1'-carbonyldiimidazole activation. The content of albumin of the albumin-fixed membrane was 121.3 mg (g membrane) -1 . The albumin-fixed dialysis membranes were used to remove protein-bound toxins, bilirubin, from the bilirubin-albumin solution. The transfer rate of bilirubin of the albumin-fixed membrane was obviously higher compared to the normal dialysis membrane. The clearance of bilirubin with the albumin-fixed membrane was 49.8%. The albumin-fixed membrane can easily be regenerated by the bovine serum albumin and NaOH solution. Regeneration of the membrane suggested good mechanical and chemical stability, as well as good clearance of bilirubin. In addition, the effects of membrane thickness and bilirubin initial concentration on the removal of bilirubin were discussed

Crystal structure of Helicobacter pylori neutrophil-activating protein with a di-nuclear ferroxidase center in a zinc or cadmium-bound form

Energy Technology Data Exchange (ETDEWEB)

Yokoyama, Hideshi, E-mail: h-yokoya@u-shizuoka-ken.ac.jp [School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan); Tsuruta, Osamu; Akao, Naoya; Fujii, Satoshi [School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan)

2012-06-15

Highlights: Black-Right-Pointing-Pointer Structures of a metal-bound Helicobacter pylori neutrophil-activating protein were determined. Black-Right-Pointing-Pointer Two zinc ions were tetrahedrally coordinated by ferroxidase center (FOC) residues. Black-Right-Pointing-Pointer Two cadmium ions were coordinated in a trigonal-bipyramidal and octahedral manner. Black-Right-Pointing-Pointer The second metal ion was more weakly coordinated than the first at the FOC. Black-Right-Pointing-Pointer A zinc ion was found in one negatively-charged pore suitable as an ion path. -- Abstract: Helicobacter pylori neutrophil-activating protein (HP-NAP) is a Dps-like iron storage protein forming a dodecameric shell, and promotes adhesion of neutrophils to endothelial cells. The crystal structure of HP-NAP in a Zn{sup 2+}- or Cd{sup 2+}-bound form reveals the binding of two zinc or two cadmium ions and their bridged water molecule at the ferroxidase center (FOC). The two zinc ions are coordinated in a tetrahedral manner to the conserved residues among HP-NAP and Dps proteins. The two cadmium ions are coordinated in a trigonal-bipyramidal and distorted octahedral manner. In both structures, the second ion is more weakly coordinated than the first. Another zinc ion is found inside of the negatively-charged threefold-related pore, which is suitable for metal ions to pass through.

A photophysical study of two fluorogen-activating proteins bound to their cognate fluorogens

Energy Technology Data Exchange (ETDEWEB)

Gaiotto, Tiziano [Los Alamos National Laboratory; Nguyen, Hau B [Los Alamos National Laboratory; Jung, Jaemyeong [Los Alamos National Laboratory; Bradbury, Andrew M [Los Alamos National Laboratory; Gnanakaran, S. [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory; Waldo, Geoffrey S [Los Alamos National Laboratory; Goodwin, Peter M [Los Alamos National Laboratory

2010-12-14

We are exploring the feasibility of using recently developed flu orogen-activating proteins (FAPs) as reporters for single-molecule imaging. FAPs are single-chain antibodies choosen to specifically bind small chromophoric molecules termed f1uorogens. Upon binding to its cognate FAP the fluorescence quantum yield of the fluorogen can increase substantially giving rise to a fluorescent complex. Based on the seminal work of Szent-Gyorgyi et al. (Nature Biotechnology, Volume 26, Number 2, pp 235-240, 2008) we have chosen to study two fluorogen-activating single-chain antibodies, HL 1.0.1-TOI and H6-MG bound to their cognate fluorogens, thiazole orange and malachite green derivatives, respectively. Here we use fluorescence correlation spectroscopy study the photophysics of these fluorescent complexes.

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...

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.

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.

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.

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.

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.

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...

High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor

DEFF Research Database (Denmark)

Cherezov, Vadim; Rosenbaum, Daniel M; Hanson, Michael A

2007-01-01

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to t...

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.

Human factor H-related protein 2 (CFHR2 regulates complement activation.

Directory of Open Access Journals (Sweden)

Hannes U Eberhardt

Full Text Available Mutations and deletions within the human CFHR gene cluster on chromosome 1 are associated with diseases, such as dense deposit disease, CFHR nephropathy or age-related macular degeneration. Resulting mutant CFHR proteins can affect complement regulation. Here we identify human CFHR2 as a novel alternative pathway complement regulator that inhibits the C3 alternative pathway convertase and terminal pathway assembly. CFHR2 is composed of four short consensus repeat domains (SCRs. Two CFHR2 molecules form a dimer through their N-terminal SCRs, and each of the two C-terminal ends can bind C3b. C3b bound CFHR2 still allows C3 convertase formation but the CFHR2 bound convertases do not cleave the substrate C3. Interestingly CFHR2 hardly competes off factor H from C3b. Thus CFHR2 likely acts in concert with factor H, as CFHR2 inhibits convertases while simultaneously allowing factor H assisted degradation by factor I.

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.

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

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.

Studying repair of a single protein-bound nick in vivo using the Flp-nick system

DEFF Research Database (Denmark)

Nielsen, Ida; Andersen, Anni Hangaard; Bjergbæk, Lotte

2012-01-01

The Flp-nick system is a simple in vivo system developed for studying the cellular responses to a protein-bound nick at a single genomic site in the budding yeast Saccharomyces cerevisiae. The Flp-nick system takes advantage of a mutant Flp recombinase that can introduce a nick at a specific Flp ...

Two-dimensional sum-frequency generation (2D SFG) reveals structure and dynamics of a surface-bound peptide

Science.gov (United States)

Laaser, Jennifer E.; Skoff, David R.; Ho, Jia-Jung; Joo, Yongho; Serrano, Arnaldo L.; Steinkruger, Jay D.; Gopalan, Padma; Gellman, Samuel H.; Zanni, Martin T.

2014-01-01

Surface-bound polypeptides and proteins are increasingly used to functionalize inorganic interfaces such as electrodes, but their structural characterization is exceedingly difficult with standard technologies. In this paper, we report the first two-dimensional sum-frequency generation (2D SFG) spectra of a peptide monolayer, which is collected by adding a mid-IR pulse shaper to a standard femtosecond SFG spectrometer. On a gold surface, standard FTIR spectroscopy is inconclusive about the peptide structure because of solvation-induced frequency shifts, but the 2D lineshapes, anharmonic shifts, and lifetimes obtained from 2D SFG reveal that the peptide is largely α-helical and upright. Random coil residues are also observed, which do not themselves appear in SFG spectra due to their isotropic structural distribution, but which still absorb infrared light and so can be detected by cross-peaks in 2D SFG spectra. We discuss these results in the context of peptide design. Because of the similar way in which the spectra are collected, these 2D SFG spectra can be directly compared to 2D IR spectra, thereby enabling structural interpretations of surface-bound peptides and biomolecules based on the well-studied structure/2D IR spectra relationships established from soluble proteins. PMID:24372101

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

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.

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.

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.

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

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.

Complement factor H-related proteins CFHR2 and CFHR5 represent novel ligands for the infection-associated CRASP proteins of Borrelia burgdorferi.

Directory of Open Access Journals (Sweden)

Corinna Siegel

2010-10-01

Full Text Available One virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASP which interact with complement regulator factor H (CFH and factor H-like protein 1 (FHL1 or factor H-related protein 1 (CFHR1. In the present study we elucidate the role of the infection-associated CRASP-3 and CRASP-5 protein to serve as ligands for additional complement regulatory proteins as well as for complement resistance of B. burgdorferi.To elucidate whether CRASP-5 and CRASP-3 interact with various human proteins, both borrelial proteins were immobilized on magnetic beads. Following incubation with human serum, bound proteins were eluted and separated by Glycine-SDS-PAGE. In addition to CFH and CFHR1, complement regulators CFHR2 and CFHR5 were identified as novel ligands for both borrelial proteins by employing MALDI-TOF. To further assess the contributions of CRASP-3 and CRASP-5 to complement resistance, a serum-sensitive B. garinii strain G1 which lacks all CFH-binding proteins was used as a valuable model for functional analyses. Both CRASPs expressed on the B. garinii outer surface bound CFH as well as CFHR1 and CFHR2 in ELISA. In contrast, live B. garinii bound CFHR1, CFHR2, and CFHR5 and only miniscute amounts of CFH as demonstrated by serum adsorption assays and FACS analyses. Further functional analysis revealed that upon NHS incubation, CRASP-3 or CRASP-5 expressing borreliae were killed by complement.In the absence of CFH and the presence of CFHR1, CFHR2 and CFHR5, assembly and integration of the membrane attack complex was not efficiently inhibited indicating that CFH in co-operation with CFHR1, CFHR2 and CFHR5 supports complement evasion of B. burgdorferi.

Interactions between macromolecule-bound antioxidants and Trolox during liposome autoxidation

DEFF Research Database (Denmark)

Celik, Ecem Evrim; Amigo Rubio, Jose Manuel; Andersen, Mogens Larsen

2017-01-01

The interactions between free and macromolecule-bound antioxidants were investigated in order to evaluate their combined effects on the antioxidant environment. Dietary fiber (DF), protein and lipid-bound antioxidants, obtained from whole wheat, soybean and olive oil products, respectively and Tr...... of logistic function was successfully used for modelling the oxidation curve of liposomes. Principal component analysis revealed two separate phases of liposome autoxidation.......The interactions between free and macromolecule-bound antioxidants were investigated in order to evaluate their combined effects on the antioxidant environment. Dietary fiber (DF), protein and lipid-bound antioxidants, obtained from whole wheat, soybean and olive oil products, respectively...... of the simple addition effects of Trolox and bound antioxidants with measured values on lipid oxidation revealed synergetic interactions for DF and refined olive oil-bound antioxidants, and antagonistic interactions for protein and extra virgin olive oil-bound antioxidants with Trolox. A generalized version...

Functions that Protect Escherichia coli from Tightly Bound DNA-Protein Complexes Created by Mutant EcoRII Methyltransferase.

Science.gov (United States)

Henderson, Morgan L; Kreuzer, Kenneth N

2015-01-01

Expression of mutant EcoRII methyltransferase protein (M.EcoRII-C186A) in Escherichia coli leads to tightly bound DNA-protein complexes (TBCs), located sporadically on the chromosome rather than in tandem arrays. The mechanisms behind the lethality induced by such sporadic TBCs are not well studied, nor is it clear whether very tight binding but non-covalent complexes are processed in the same way as covalent DNA-protein crosslinks (DPCs). Using 2D gel electrophoresis, we found that TBCs induced by M.EcoRII-C186A block replication forks in vivo. Specific bubble molecules were detected as spots on the 2D gel, only when M.EcoRII-C186A was induced, and a mutation that eliminates a specific EcoRII methylation site led to disappearance of the corresponding spot. We also performed a candidate gene screen for mutants that are hypersensitive to TBCs induced by M.EcoRII-C186A. We found several gene products necessary for protection against these TBCs that are known to also protect against DPCs induced with wild-type M.EcoRII (after 5-azacytidine incorporation): RecA, RecBC, RecG, RuvABC, UvrD, FtsK, XerCD and SsrA (tmRNA). In contrast, the RecFOR pathway and Rep helicase are needed for protection against TBCs but not DPCs induced by M.EcoRII. We propose that stalled fork processing by RecFOR and RecA promotes release of tightly bound (but non-covalent) blocking proteins, perhaps by licensing Rep helicase-driven dissociation of the blocking M.EcoRII-C186A. Our studies also argued against the involvement of several proteins that might be expected to protect against TBCs. We took the opportunity to directly compare the sensitivity of all tested mutants to two quinolone antibiotics, which target bacterial type II topoisomerases and induce a unique form of DPC. We uncovered rep, ftsK and xerCD as novel quinolone hypersensitive mutants, and also obtained evidence against the involvement of a number of functions that might be expected to protect against quinolones.

Functions that Protect Escherichia coli from Tightly Bound DNA-Protein Complexes Created by Mutant EcoRII Methyltransferase.

Directory of Open Access Journals (Sweden)

Morgan L Henderson

Full Text Available Expression of mutant EcoRII methyltransferase protein (M.EcoRII-C186A in Escherichia coli leads to tightly bound DNA-protein complexes (TBCs, located sporadically on the chromosome rather than in tandem arrays. The mechanisms behind the lethality induced by such sporadic TBCs are not well studied, nor is it clear whether very tight binding but non-covalent complexes are processed in the same way as covalent DNA-protein crosslinks (DPCs. Using 2D gel electrophoresis, we found that TBCs induced by M.EcoRII-C186A block replication forks in vivo. Specific bubble molecules were detected as spots on the 2D gel, only when M.EcoRII-C186A was induced, and a mutation that eliminates a specific EcoRII methylation site led to disappearance of the corresponding spot. We also performed a candidate gene screen for mutants that are hypersensitive to TBCs induced by M.EcoRII-C186A. We found several gene products necessary for protection against these TBCs that are known to also protect against DPCs induced with wild-type M.EcoRII (after 5-azacytidine incorporation: RecA, RecBC, RecG, RuvABC, UvrD, FtsK, XerCD and SsrA (tmRNA. In contrast, the RecFOR pathway and Rep helicase are needed for protection against TBCs but not DPCs induced by M.EcoRII. We propose that stalled fork processing by RecFOR and RecA promotes release of tightly bound (but non-covalent blocking proteins, perhaps by licensing Rep helicase-driven dissociation of the blocking M.EcoRII-C186A. Our studies also argued against the involvement of several proteins that might be expected to protect against TBCs. We took the opportunity to directly compare the sensitivity of all tested mutants to two quinolone antibiotics, which target bacterial type II topoisomerases and induce a unique form of DPC. We uncovered rep, ftsK and xerCD as novel quinolone hypersensitive mutants, and also obtained evidence against the involvement of a number of functions that might be expected to protect against quinolones.

Modelling Ca2+ bound Troponin in Excitation Contraction Coupling

Directory of Open Access Journals (Sweden)

Henry G. Zot

2016-09-01

Full Text Available To explain disparate decay rates of cytosolic Ca2+ and structural changes in the thin filaments during a twitch, we model the time course of Ca2+ bound troponin (Tn resulting from the free Ca2+ transient of fast skeletal muscle. In fibers stretched beyond overlap, the decay of Ca2+ as measured by a change in fluo 3 fluorescence is significantly slower than the intensity decay of the meridional 1/38.5 nm-1 reflection of Tn; this is not simply explained by considering only the Ca2+ binding properties of Tn alone (Matsuo, T., Iwamoto, H., and Yagi, N. (2010. Biophys. J. 99, 193-200. We apply a comprehensive model that includes the known Ca2+ binding properties of Tn in the context of the thin filament with and without cycling crossbridges. Calculations based on the model predict that the transient of Ca2+ bound Tn correlates with either the fluo 3 time course in muscle with overlapping thin and thick filaments or the intensity of the meridional 1/38.5 nm-1 reflection in overstretched muscle. Hence, cycling crossbridges delay the dissociation of Ca2+ from Tn. Correlation with the fluo 3 fluorescence change is not causal given that the transient of Ca2+ bound Tn depends on sarcomere length, whereas the fluo-3 fluorescence change does not. Transient positions of tropomyosin calculated from the time course of Ca2+ bound Tn are in reasonable agreement with the transient of measured perturbations of the Tn repeat in overlap and non-overlap muscle preparations.

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

Science.gov (United States)

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.

Markers of protein oxidation

DEFF Research Database (Denmark)

Headlam, Henrietta A; Davies, Michael Jonathan

2004-01-01

Exposure of proteins to radicals in the presence of O2 gives both side-chain oxidation and backbone fragmentation. These processes can be interrelated, with initial side-chain oxidation giving rise to backbone damage via transfer reactions. We have shown previously that alkoxyl radicals formed...... of this process depends on the extent of oxidation at C-3 compared with other sites. HO*, generated by gamma radiolysis, gave the highest total carbonyl yield, with protein-bound carbonyls predominating over released. In contrast, metal ion/H2O2 systems, gave more released than bound carbonyls, with this ratio...... modulated by EDTA. This is ascribed to metal ion-protein interactions affecting the sites of initial oxidation. Hypochlorous acid gave low concentrations of released carbonyls, but high yields of protein-bound material. The peroxyl radical generator 2,2'-azobis(2-amidinopropane) hydrochloride...

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.

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.

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.

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.

G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter

DEFF Research Database (Denmark)

Dou, Q P; Zhao, S; Levin, A H

1994-01-01

report that MT2 includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following evidence. (i) MT2 bound specifically to an affinity-purified fusion human E2F protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound specifically to similar or identical nuclear protein complexes...... complexes were also investigated. Studies using specific antibodies revealed that p107, a retinoblastoma-like protein, was present in both E2F-G0/G1 and E2F.S, whereas cyclin E.cyclin A.cdk2 were only present in E2F.S complex(es). These data suggest that removal of the p107-containing E2F.G0/G1 complex...

Candidate Genes for Testicular Cancer Evaluated by In Situ Protein Expression Analyses on Tissue Microarrays

Directory of Open Access Journals (Sweden)

Rolf I. Skotheim

2003-09-01

Full Text Available By the use of high-throughput molecular technologies, the number of genes and proteins potentially relevant to testicular germ cell tumor (TGCT and other diseases will increase rapidly. In a recent transcriptional profiling, we demonstrated the overexpression of GRB7 and JUP in TGCTs, confirmed the reported overexpression of CCND2. We also have recent evidences for frequent genetic alterations of FHIT and epigenetic alterations of MGMT. To evaluate whether the expression of these genes is related to any clinicopathological variables, we constructed a tissue microarray with 510 testicular tissue cores from 279 patients diagnosed with TGCT, covering various histological subgroups and clinical stages. By immunohistochemistry, we found that JUP, GRB7, CCND2 proteins were rarely present in normal testis, but frequently expressed at high levels in TGCT. Additionally, all premalignant intratubular germ cell neoplasias were JUP-immunopositive. MGMT and FHIT were expressed by normal testicular tissues, but at significantly lower frequencies in TGCT. Except for CCND2, the expressions of all markers were significantly associated with various TGCT subtypes. In summary, we have developed a high-throughput tool for the evaluation of TGCT markers, utilized this to validate five candidate genes whose protein expressions were indeed deregulated in TGCT.

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.

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

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).

Analysis of SiO2 nanoparticles binding proteins in rat blood and brain homogenate

Directory of Open Access Journals (Sweden)

Shim KH

2014-12-01

Full Text Available Kyu Hwan Shim,1 John Hulme,1 Eun Ho Maeng,2 Meyoung-Kon Kim,3 Seong Soo A An1 1Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Sungnam-si, 2Department of Analysis, KTR, Kimpo, Gyeonggi-do, 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea Abstract: A multitude of nanoparticles, such as titanium oxide (TiO2, zinc oxide, aluminum oxide, gold oxide, silver oxide, iron oxide, and silica oxide, are found in many chemical, cosmetic, pharmaceutical, and electronic products. Recently, SiO2 nanoparticles were shown to have an inert toxicity profile and no association with an irreversible toxicological change in animal models. Hence, exposure to SiO2 nanoparticles is on the increase. SiO2 nanoparticles are routinely used in numerous materials, from strengthening filler for concrete and other construction composites, to nontoxic platforms for biomedical application, such as drug delivery and theragnostics. On the other hand, recent in vitro experiments indicated that SiO2 nanoparticles were cytotoxic. Therefore, we investigated these nanoparticles to identify potentially toxic pathways by analyzing the adsorbed protein corona on the surface of SiO2 nanoparticles in the blood and brain of the rat. Four types of SiO2 nanoparticles were chosen for investigation, and the protein corona of each type was analyzed using liquid chromatography-tandem mass spectrometry technology. In total, 115 and 48 plasma proteins from the rat were identified as being bound to negatively charged 20 nm and 100 nm SiO2 nanoparticles, respectively, and 50 and 36 proteins were found for 20 nm and 100 nm arginine-coated SiO2 nanoparticles, respectively. Higher numbers of proteins were adsorbed onto the 20 nm sized SiO2 nanoparticles than onto the 100 nm sized nanoparticles regardless of charge. When proteins were compared between the two charges, higher numbers of proteins were

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

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

An Upper Bound on the Entropy of Constrained 2d Fields

DEFF Research Database (Denmark)

Forchhammer, Søren; Justesen, Jørn

1998-01-01

An upper bound on the entropy of constrained 2D fields is presented. The constraints have to be symmetric in (at least) one of the two directions. The bound generalizes (in a weaker form) the bound of Calkin and Wilf (see SIAM Journal of Discrete Mathematics, vol.11, p.54-60, 1998) which is valid...

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).

Structural organization of poliovirus RNA replication is mediated by viral proteins of the P2 genomic region

International Nuclear Information System (INIS)

Bienz, K.; Egger, D.; Troxler, M.; Pasamontes, L.

1990-01-01

Transcriptionally active replication complexes bound to smooth membrane vesicles were isolated from poliovirus-infected cells. In electron microscopic, negatively stained preparations, the replication complex appeared as an irregularly shaped, oblong structure attached to several virus-induced vesicles of a rosettelike arrangement. Electron microscopic immunocytochemistry of such preparations demonstrated that the poliovirus replication complex contains the proteins coded by the P2 genomic region (P2 proteins) in a membrane-associated form. In addition, the P2 proteins are also associated with viral RNA, and they can be cross-linked to viral RNA by UV irradiation. Guanidine hydrochloride prevented the P2 proteins from becoming membrane bound but did not change their association with viral RNA. The findings allow the conclusion that the protein 2C or 2C-containing precursor(s) is responsible for the attachment of the viral RNA to the vesicular membrane and for the spatial organization of the replication complex necessary for its proper functioning in viral transcription. A model for the structure of the viral replication complex and for the function of the 2C-containing P2 protein(s) and the vesicular membranes is proposed

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

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

Scanning a DNA molecule for bound proteins using hybrid magnetic and optical tweezers.

Directory of Open Access Journals (Sweden)

Marijn T J van Loenhout

Full Text Available The functional state of the genome is determined by its interactions with proteins that bind, modify, and move along the DNA. To determine the positions and binding strength of proteins localized on DNA we have developed a combined magnetic and optical tweezers apparatus that allows for both sensitive and label-free detection. A DNA loop, that acts as a scanning probe, is created by looping an optically trapped DNA tether around a DNA molecule that is held with magnetic tweezers. Upon scanning the loop along the λ-DNA molecule, EcoRI proteins were detected with ~17 nm spatial resolution. An offset of 33 ± 5 nm for the detected protein positions was found between back and forwards scans, corresponding to the size of the DNA loop and in agreement with theoretical estimates. At higher applied stretching forces, the scanning loop was able to remove bound proteins from the DNA, showing that the method is in principle also capable of measuring the binding strength of proteins to DNA with a force resolution of 0.1 pN/[Formula: see text]. The use of magnetic tweezers in this assay allows the facile preparation of many single-molecule tethers, which can be scanned one after the other, while it also allows for direct control of the supercoiling state of the DNA molecule, making it uniquely suitable to address the effects of torque on protein-DNA interactions.

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.

Effects of solution chemistry and aging time on prion protein adsorption and replication of soil-bound prions.

Directory of Open Access Journals (Sweden)

Samuel E Saunders

2011-04-01

Full Text Available Prion interactions with soil may play an important role in the transmission of chronic wasting disease (CWD and scrapie. Prions are known to bind to a wide range of soil surfaces, but the effects of adsorption solution chemistry and long-term soil binding on prion fate and transmission risk are unknown. We investigated HY TME prion protein (PrP(Sc adsorption to soil minerals in aqueous solutions of phosphate buffered saline (PBS, sodium chloride, calcium chloride, and deionized water using western blotting. The replication efficiency of bound prions following adsorption in these solutions was also evaluated by protein misfolding cyclic amplification (PMCA. Aging studies investigated PrP(Sc desorption and replication efficiency up to one year following adsorption in PBS or DI water. Results indicate that adsorption solution chemistry can affect subsequent prion replication or desorption ability, especially after incubation periods of 30 d or longer. Observed effects were minor over the short-term (7 d or less. Results of long-term aging experiments demonstrate that unbound prions or prions bound to a diverse range of soil surfaces can readily replicate after one year. Our results suggest that while prion-soil interactions can vary with solution chemistry, prions bound to soil could remain a risk for transmitting prion diseases after months in the environment.

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).

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

Efficacy of an adapted granzyme B-based anti-CD30 cytolytic fusion protein against PI-9-positive classical Hodgkin lymphoma cells in a murine model

International Nuclear Information System (INIS)

Schiffer, S; Hansen, H P; Hehmann-Titt, G; Huhn, M; Fischer, R; Barth, S; Thepen, T

2013-01-01

Tumors develop when infiltrating immune cells contribute growth stimuli, and cancer cells are selected to survive within such a cytotoxic microenvironment. One possible immune-escape mechanism is the upregulation of PI-9 (Serpin B9) within cancer cells. This serine proteinase inhibitor selectively inactivates apoptosis-inducing granzyme B (GrB) from cytotoxic granules of innate immune cells. We demonstrate that most classical Hodgkin lymphoma (cHL)-derived cell lines express PI-9, which protects them against the GrB attack and thereby renders them resistant against GrB-based immunotherapeutics. To circumvent this disadvantage, we developed PI-9-insensitive human GrB mutants as fusion proteins to target the Hodgkin-selective receptor CD30. In contrast to the wild-type GrB, a R201K point-mutated GrB construct most efficiently killed PI-9-positive and -negative cHL cells. This was tested in vitro and also in vivo whereby a novel optical imaging-based tumor model with HL cell line L428 was applied. Therefore, this variant, as part of the next generation immunotherapeutics, also named cytolytic fusion proteins showing reduced immunogenicity, is a promising molecule for (targeted) therapy of patients with relapsing malignancies, such as cHL, and possibly other PI-9-positive malignancies, such as breast or lung carcinoma

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