568 research outputs found

    Complete RXTE Spectral Observations of the Black Hole X-ray Nova XTE J1550-564

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    We report on the X-ray spectral behavior of the exceptionally bright X-ray nova XTE J1550-564 during its 1998-99 outburst. Our study is based on 209 pointed observations using the PCA and HEXTE instruments onboard the Rossi X-ray Timing Explorer spanning 250 days and covering the entire double-peaked eruption that occurred from 1998 September until 1999 May. The spectra are fit to a model including multicolor blackbody disk and power-law components. The source is observed in the very high and high/soft outburst states of black hole X-ray novae. During the very high state, when the power-law component dominated the spectrum, the inner disk radius is observed to vary by more than an order of magnitude; the radius decreased by a factor of 16 in one day during a 6.8 Crab flare. If the larger of these observed radii is taken to be the last stable orbit, then the smaller observed radius would imply that the inner edge of the disk is inside the event horizon! However, we conclude that the apparent variations of the inner disk radius observed during periods of increased power-law emission are probably caused by the failure of the multicolor disk/power-law model; the actual physical radius of the inner disk may remain fairly constant. This interpretation is supported by the fact that the observed inner disk radius remains approximately constant over 120 days in the high state, when the power-law component is weak, even though the disk flux and total flux vary by an order of magnitude. The mass of the black hole inferred by equating the approximately constant inner disk radius observed in the high/soft state with the last stable orbit for a Schwarzschild black hole is M_BH = 7.4 M_sun (D/6 kpc) (cos i)^{-1/2}.Comment: Submitted to ApJ, 20 pages including 6 figures + 4 large table

    Substituted Lactam and Cyclic Azahemiacetals Modulate Pseudomonas aeruginosa Quorum Sensing

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    Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence that is critical for establishing infection. The most common QS signaling molecule used by Gram-negative bacteria are acylhomoserine lactones. The development of non-native acylhomoserine lactone (AHL) ligands has emerged as a promising new strategy to inhibit QS in Gram-negative bacteria. In this work, we have synthesized a set of optically pure γ-lactams and their reduced cyclic azahemiacetal analogues, bearing the additional alkylthiomethyl substituent, and evaluated their effect on the AHL-dependent Pseudomonas aeruginosa las and rhl QS pathways. The concentration of these ligands and the simple structural modification such as the length of the alkylthio substituent has notable effect on activity. The γ-lactam derivatives with nonylthio or dodecylthio chains acted as inhibitors of las signaling with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent was found to strongly inhibit both las and rhl signaling at higher concentrations while the propylthio analogue strongly stimulated the las QS system at lower concentrations

    Broadband X-ray spectrum of XTE J1550-564 during 2003 outburst

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    Results of broadband INTEGRAL and RXTE observations of the Galactic microquasar XTE J1550-564 during outburst in spring 2003 are presented. During the outburst the source was found in a canonical low/hard spectral state.Comment: 5 pages, 3 figures. Accepted for publication in Astronomy Letter

    Investigation of reactions postulated to occur during inhibition of ribonucleotide reductases by 2 0 -azido-2 0 -deoxynucleotides

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    a b s t r a c t Model 3 0 -azido-3 0 -deoxynucleosides with thiol or vicinal dithiol substituents at C2 0 or C5 0 were synthesized to study reactions postulated to occur during inhibition of ribonucleotide reductases by 2 0 -azido-2 0 -deoxynucleotides. Esterification of 5 0 -(tert-butyldiphenylsilyl)-3 0 -azido-3 0 -deoxyadenosine and 3 0 -azido-3 0 -deoxythymidine (AZT) with 2,3-S-isopropylidene-2,3-dimercaptopropanoic acid or N-Boc-Strityl-L-cysteine and deprotection gave 3 0 -azido-3 0 -deoxy-2 0 -O-(2,3-dimercaptopropanoyl or cysteinyl) adenosine and the 3 0 -azido-3 0 -deoxy-5 0 -O-(2,3-dimercaptopropanoyl or cysteinyl)thymidine analogs. Density functional calculations predicted that intramolecular reactions between generated thiyl radicals and an azido group on such model compounds would be exothermic by 33.6e41.2 kcal/mol and have low energy barriers of 10.4e13.5 kcal/mol. Reduction of the azido group occurred to give 3 0 -amino-3 0 -deoxythymidine, which was postulated to occur with thiyl radicals generated by treatment of 3 0 -azido-3 0 -deoxy-5 0 -O-(2,3-dimercaptopropanoyl)thymidine with 2,2 0 -azobis-(2-methyl-2-propionamidine) dihydrochloride. Gamma radiolysis of N 2 O-saturated aqueous solutions of AZT and cysteine produced 3 0 -amino-3 0 -deoxythymidine and thymine most likely by both radical and ionic processes

    Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.

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    BACKGROUND Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT -VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMVTT -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP-compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development. METHOD The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut. RESULTS A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity. CONCLUSIONS Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting

    High-energy observations of the state transition of the X-ray nova and black hole candidate XTE J1720-318

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    We report the results of extensive high-energy observations of the X-ray transient and black hole candidate XTE J1720-318 performed with INTEGRAL, XMM-Newton and RXTE. The source, which underwent an X-ray outburst in 2003 January, was observed in February in a spectral state dominated by a soft component with a weak high-energy tail. The XMM-Newton data provided a high column density Nh of 1.2*e22 cm^{-2} which suggests that the source lies at the Galactic Centre distance. The simultaneous RXTE and INTEGRAL Target of Opportunity observations allowed us to measure the weak and steep tail, typical of a black-hole binary in the so-called High/Soft State. We then followed the evolution of the source outburst over several months using the INTEGRAL Galactic Centre survey observations. The source became active again at the end of March: it showed a clear transition towards a much harder state, and then decayed to a quiescent state after April. In the hard state, the source was detected up to 200 keV with a power law index of 1.9 and a peak luminosity of 7*e36 erg s^{-1} in the 20-200 keV band, for an assumed distance of 8 kpc. We conclude that XTE J1720-318 is indeed a new member of the black hole X-ray novae class which populate our galactic bulge and we discuss its properties in the frame of the spectral models used for transient black hole binaries.Comment: 10 pages, 7 figures, 2 tables, Accepted for publication in Astronomy & Astrophysic

    Energy Dependence of a Low Frequency QPO in GRS 1915+105

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    We analyze a set of three RXTE Target of Opportunity observations of the Galactic microquasar GRS 1915+105, observed on April 2000, during a multi-wavelength campaign. During the three observations, a strong, variable low frequency (2-9 Hz) quasi periodic oscillation (hereafter QPO), often referred to as the ubiquitous QPO, is detected together with its first harmonic. We study the spectral properties of both features, and show that : 1) their frequency variations are better correlated with the soft X-ray flux (2-5 keV), favoring thus the location of the QPO in the accretion disk; 2) the QPO affects more the hard X-rays, usually taken as the signature of an inverse compton scattering of the soft photons in a corona; 3) the fundamental and its harmonic do not behave in the same manner: the fundamental sees its power increase with the energy up to 40 keV, whereas the harmonic increases up to 10\sim 10 keV. The results presented here could find an explanation in the context of the Accretion-Ejection Instability, which could appear as a rotating spiral or hot point located in the disk, between its innermost edge and the corotation radius. The presence of the harmonic could then be a signature of the non-linear behavior of the instability. The high-energy (>40 keV) decrease of the fundamental would favor an interpretation where most or all of the quasi-periodic modulation at high energies comes, not from the comptonized corona as usually assumed, but from a hot point in the optically thick diskComment: 8 pages, 7 figures, accepted for publication in Astronomy and Astrophysic

    States and transitions in black-hole binaries

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    With the availability of the large database of black-hole transients from the Rossi X-Ray Timing Explorer, the observed phenomenology has become very complex. The original classification of the properties of these systems in a series of static states sorted by mass accretion rate proved not to be able to encompass the new picture. I outline here a summary of the current situation and show that a coherent picture emerges when simple properties such as X-ray spectral hardness and fractional variability are considered. In particular, fast transition in the properties of the fast time variability appear to be crucial to describe the evolution of black-hole transients. Based on this picture, I present a state-classification which takes into account the observed transitions. I show that, in addition to transients systems, other black-hole binaries and Active Galactic Nuclei can be interpreted within this framework. The association between these states and the physics of the accretion flow around black holes will be possible only through modeling of the full time evolution of galactic transient systems.Comment: 30 pages, 11 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009
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