568 research outputs found
Complete RXTE Spectral Observations of the Black Hole X-ray Nova XTE J1550-564
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
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
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
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.
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
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Environmental SLAPPs in the UK: threat or opportunity?
Strategic lawsuits against public participation (SLAPPs) brought against the environmental movement in the UK since the 1990s are examined. SLAPPs, a form of Green backlash, have been mobilised across a wide range of policy areas that have seen vigorous campaigning and protest by the movement, including roads, GMOs and, more recently, climate change. SLAPPs are typically regarded as a threat, designed to close down democratic free speech and protest. However, in the UK, there are some notable cases where the environmental movement has been able to use agency to convert what may appear as a legal threat into a positive legal or media opportunity
High-energy observations of the state transition of the X-ray nova and black hole candidate XTE J1720-318
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
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 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
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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