We report on a Neutron star Interior Composition Explorer (NICER) observation of the Galactic X-ray binary and stellar-mass black hole candidate, MAXI J1535−571. The source was likely observed in an ..."intermediate" or "very high" state, with important contributions from both an accretion disk and hard X-ray corona. The 2.3-10 keV spectrum shows clear hallmarks of relativistic disk reflection. Fits with a suitable model strongly indicate a near-maximal spin parameter of and a disk that extends close to the innermost stable circular orbit, (1 statistical errors). In addition to the relativistic spectrum from the innermost disk, a relatively narrow Fe K emission line is also required. The resolution of NICER reveals that the narrow line may be asymmetric, indicating a specific range of emission radii. Fits with a relativistic line model suggest an inner radius of for the putative second reflection geometry; full reflection models suggest that radii a few times larger are possible. The origin of the narrow line is uncertain, but a warp likely provides the most physically plausible explanation. We discuss our results in terms of the potential for NICER to reveal new features of the inner and intermediate accretion disk around black holes.
Cyclosporine, everolimus, and tacrolimus are the cornerstone of immunosuppressive therapy in renal transplantation. These drugs are characterized by narrow therapeutic windows, highly variable ...pharmacokinetics (PK), and metabolism by CYP3A enzymes. Recently, the decreased activity allele, CYP3A4*22, was described as a potential predictive marker for CYP3A4 activity. This study investigated the effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on cyclosporine, everolimus, and tacrolimus PK in renal transplant patients. CYP3A4*22 carriers showed a significant lower clearance for cyclosporine (−15%), and a trend was observed for everolimus (−7%) and tacrolimus (−16%). Patients carrying at least one CYP3A5*1 allele had 1.5‐fold higher tacrolimus clearance compared with noncarriers; however, CYP3A5*3 appeared to be nonpredictive for everolimus and cyclosporine. CYP3A combined genotype did not significantly improve prediction of clearance compared with CYP3A5*3 or CYP3A4*22 alone. These data suggest that dose individualization of cyclosporine, everolimus, or tacrolimus therapy based on CYP3A4*22 is not indicated.
CPT: Pharmacometrics Systems Pharmacology (2014); 3, e100; doi:10.1038/psp.2013.78; published online 12 February 2014
ABSTRACT
During a 2018 outburst, the black hole X-ray binary MAXI J1820 + 070 was comprehensively monitored at multiple wavelengths as it underwent a hard to soft state transition. During this ...transition, a rapid evolution in X-ray timing properties and a short-lived radio flare were observed, both of which were linked to the launching of bi-polar, long-lived relativistic ejecta. We provide a detailed analysis of two Very Long Baseline Array observations, using both time binning and a new dynamic phase centre tracking technique to mitigate the effects of smearing when observing fast-moving ejecta at high angular resolution. We identify a second, earlier ejection, with a lower proper motion of 18.0 ± 1.1 mas d−1. This new jet knot was ejected 4 ± 1 h before the beginning of the rise of the radio flare, and 2 ± 1 h before a switch from type-C to type-B X-ray quasi-periodic oscillations (QPOs). We show that this jet was ejected over a period of ∼6 h and thus its ejection was contemporaneous with the QPO transition. Our new technique locates the original, faster ejection in an observation in which it was previously undetected. With this detection, we revised the fits to the proper motions of the ejecta and calculated a jet inclination angle of (64 ± 5)°, and jet velocities of $0.97_{-0.09}^{+0.03}c$ for the fast-moving ejecta (Γ > 2.1) and (0.30 ± 0.05)c for the newly identified slow-moving ejection (Γ = 1.05 ± 0.02). We show that the approaching slow-moving component is predominantly responsible for the radio flare, and is likely linked to the switch from type-C to type-B QPOs, while no definitive signature of ejection was identified for the fast-moving ejecta.
•The gratitude model of body appreciation provided a good fit to the data for women.•Gratitude had a strong direct effect on body appreciation.•This effect was also indirect, via lower appearance ...self-worth and body comparison.•Body appreciation accounted for 88% of gratitude’s relationship with intuitive eating.•This relationship was also mediated by lower appearance self-worth and eating comparison.
Although researchers and clinicians recognize the importance of positive body image for women’s well-being, development of theoretical frameworks for understanding positive body image has not kept pace with research documenting its many benefits. The present study proposed and tested a comprehensive model linking gratitude, contingent self-worth, social comparison, body appreciation, and intuitive eating. Path analysis indicated that this model fit the data for a sample of college and online community women (N = 263). Gratitude was indirectly linked to body appreciation via lower investment in self-worth based on appearance and others’ approval, and via lower engagement in eating and body comparison. Gratitude had a strong direct effect on body appreciation, and body appreciation accounted for a large portion (88%) of gratitude’s relationship with intuitive eating. These results provide strong preliminary support for the model, revealing that gratitude, which can be improved via intervention, plays a key role in body appreciation.
We report on X-ray observations of the black hole candidate GX 339−4 during its 2006/2007 outburst. The hardness–intensity diagram (HID) of all RXTE/Proportional Counter Array data combined shows a ...q-shaped track similar to that observed in previous outbursts. The evolution through the HID suggests that in the early phase of the outburst the source underwent a sequence of state transitions, from the hard to the soft state, which is supported by our timing analysis. Broad-band (4–200 keV) spectra, fitted with an exponentially cut-off power law, show that the hard spectral component steepens during the transition from the hard to the soft state. The high-energy cut-off decreased monotonically from 120 to 60 keV during the brightening of the hard state, but again increased to 100 keV during the softening in the hard intermediate state. In the short-lived soft intermediate state the cut-off energy was ∼130 keV, but was no longer detected in the soft state. This is one of the first times that the high-energy cut-off has been followed in such detail across several state transitions. We find that in comparison to several other spectral parameters, the cut-off energy changes more rapidly, just like the timing properties. The observed behaviour of the high-energy cut-off of GX 339−4 is also similar to that observed with RXTE–INTEGRAL–Swift during the 2005 outburst of GRO J1655−40. These results constitute a valuable reference to be considered when testing theoretical models for the production of the hard component in these systems.
Highlights • ACT is an option for the treatment of anxiety and OCD-spectrum disorders. • Meta-analyses show small to large correlations between AAQ and anxiety measures. • All outcome studies of ACT ...for anxiety and OCD-spectrum disorders are reviewed. • Preliminary meta-analyses show ACT is equally effective to CBT.
An introduction to a series of essays honoring Erich Meyerhoff (1919-2015), AHIP, FMLA, who was active in and contributed to the Medical Library Association for generations.
The Galactic black hole X-ray binary MAXI J1820+070 had a bright outburst in 2018 when it became the second brightest X-ray source in the sky. It was too bright for X-ray CCD instruments such as ...XMM–Newton and Chandra, but was well observed by photon counting instruments such as Neutron star Inner Composition Explorer (NICER) and Nuclear Spectroscopic Telescope Array (NuSTAR). We report here on the discovery of an excess emission component during the soft state. It is best modelled with a blackbody spectrum in addition to the regular disc emission, modelled as either diskbb or kerrbb. Its temperature varies from about 0.9 to 1.1 keV, which is about 30–80 per cent higher than the inner disc temperature of diskbb. Its flux varies between 4 and 12 per cent of the disc flux. Simulations of magnetized accretion discs have predicted the possibility of excess emission associated with a non-zero torque at the innermost stable circular orbit (ISCO) about the black hole, which, from other NuSTAR studies, lies at about 5 gravitational radii or about 60 km (for a black hole, mass is 8Msun). In this case, the emitting region at the ISCO has a width varying between 1.3 and 4.6 km and would encompass the start of the plunge region where matter begins to fall freely into the black hole.
We present the discovery of a low-frequency 5.7 Hz quasi-periodic oscillation (QPO) feature in observations of the black hole X-ray binary MAXI J1535-571 in its soft-intermediate state, obtained in ...2017 September-October by the Neutron Star Interior Composition Explorer. The feature is relatively broad (compared to other low-frequency QPOs; quality factor Q 2) and weak (1.9% rms in 3-10 keV), and is accompanied by a weak harmonic and low-amplitude broadband noise. These characteristics identify it as a weak Type A/B QPO, similar to ones previously identified in the soft-intermediate state of the transient black hole X-ray binary XTE J1550-564. The lag-energy spectrum of the QPO shows increasing soft lags toward lower energies, approaching 50 ms at 1 keV (with respect to a 3-10 keV continuum). This large phase shift has similar amplitude but opposite sign to that seen in Rossi X-Ray Timing Explorer data for a Type B QPO from the transient black hole X-ray binary GX 339-4. Previous phase-resolved spectroscopy analysis of the Type B QPO in GX 339-4 pointed toward a precessing jet-like corona illuminating the accretion disk as the origin of the QPO signal. We suggest that this QPO in MAXI J1535-571 may have the same origin, with the different lag sign depending on the scale height of the emitting region and the observer inclination angle.
Single-molecule correlated chemical probing of RNA Homan, Philip J.; Favorov, Oleg V.; Lavender, Christopher A. ...
Proceedings of the National Academy of Sciences,
09/2014, Volume:
111, Issue:
38
Journal Article
Peer reviewed
Open access
Significance RNA molecules function as the central conduit of information transfer in biology. To do this, they encode information both in their sequences and in their higher-order structures. ...Understanding the higher-order structure of RNA remains challenging. In this work we devise a simple, experimentally concise, and accurate approach for examining higher-order RNA structure by converting widely used massively parallel sequencing into an easily implemented single-molecule experiment for detecting through-space interactions and multiple conformations. We then use this experiment to analyze higher-order RNA structure, detect biologically important hidden states, and refine accurate three-dimensional structure models.
Complex higher-order RNA structures play critical roles in all facets of gene expression; however, the through-space interaction networks that define tertiary structures and govern sampling of multiple conformations are poorly understood. Here we describe single-molecule RNA structure analysis in which multiple sites of chemical modification are identified in single RNA strands by massively parallel sequencing and then analyzed for correlated and clustered interactions. The strategy thus identifies RNA interaction groups by mutational profiling (RING-MaP) and makes possible two expansive applications. First, we identify through-space interactions, create 3D models for RNAs spanning 80–265 nucleotides, and characterize broad classes of intramolecular interactions that stabilize RNA. Second, we distinguish distinct conformations in solution ensembles and reveal previously undetected hidden states and large-scale structural reconfigurations that occur in unfolded RNAs relative to native states. RING-MaP single-molecule nucleic acid structure interrogation enables concise and facile analysis of the global architectures and multiple conformations that govern function in RNA.
PDF
