We present the results of an extensive timing analysis of the 1999 outburst of the soft X-ray transient and black hole candidate XTE J1859+226 as observed with the Rossi X-Ray Timing Explorer. Three ...main different types of low frequency (1-9 Hz) quasi-periodic oscillations (QPOs) were observed and classified, strengthening the general picture that is emerging for the variability properties of black hole X-ray binaires. Rapid transitions between different power spectral shapes were observed and their link with the count rate was studied. Furthermore, we show that a frequency of ~6 Hz seems to hold a particular place: one of the three QPO types we found was very stable when at this frequency, as it happens in Z sources as well. The coherence of its subharmonic peak was higher when the fundamental was close to 6 Hz, thus suggesting the presence of some resonance at this frequency.
Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with ...hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post‐transplant. We analyzed glomerular filtration rate (GFR, 125I‐iothalamate) and effective renal plasma flow (ERPF, 131I‐hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long‐term impact of BMI and renal hemodynamics were explored by Cox‐regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r2 of the model 0.275) and FF (adjusted r2 of the model 0.158). This association was not explained by diabetes mellitus. On Cox‐regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death‐censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent–efferent balance. Mechanisms underlying the long‐term prognostic impact of hyperfiltration deserve further exploration.
This study of the relationship between recipient BMI and renal hemodynamics one year post‐transplant found that higher recipient BMI is associated with higher GFR and filtration fraction.
We studied the low-frequency quasi-periodic oscillations (LFQPOs) in the black hole GROJ1655-40 during the 2005 outburst, using data from the Rossi X-ray Timing Explorer. All LFQPOs could be ...identified as either type B or type C using previously proposed classification schemes. In the soft state of the outburst the type-C LFQPOs reached frequencies that are among the highest ever seen for LFQPOs in black holes. At the peak of the outburst, in the ultraluminous state, the power spectrum showed two simultaneous, non-harmonically related peaks which we identified as a type-B and a type-C QPO. The simultaneous presence of a type-C and type-B QPO shows that at least two of the three known LFQPO types are intrinsically different and likely the result of distinct physical mechanisms. We also studied the properties of a broad peaked noise component in the power spectra of the ultraluminous state. This noise component becomes more coherent with count rate and there are strong suggestions that it evolves into a type-B QPO at the highest observed count rates. PUBLICATION ABSTRACT
Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium ...intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume.
We present optical, X-ray and radio observations of the black hole transient (BHT) XTE J1752−223 towards and in quiescence. Optical photometry shows that the quiescent magnitude of XTE J1752−223 is ...fainter than 24.4 mag in the i′ band. A comparison with measurements of the source during its 2009-2010 outburst shows that the outburst amplitude is more than 8 mag in the i′ band. Known X-ray properties of the source combined with the faintness of the quiescence optical counterpart and the large outburst optical amplitude point towards a short orbital-period system (P
orb≲ 6.8 h) with an M type (or later) mass donor, at a distance of 3.5 ≲d≲ 8 kpc. Simultaneous X-ray and radio data were collected with Chandra and the Expanded Very Large Array (EVLA), allowing constraints to be placed on the quiescent X-ray and radio flux of XTE J1752−223. Furthermore, using data covering the final stage of the outburst decay, we investigated the low-luminosity end of the X-ray-radio correlation for this source and compared it with other BHTs. We found that XTE J1752−223 adds to the number of outliers with respect to the 'standard' X-ray-radio luminosity relation. Furthermore, XTE J1752−223 is the second source, after the BHT H1743−322, that shows a transition from the region of the outliers towards the 'standard' correlation at low luminosity. Finally, we report on a faint, variable X-ray source we discovered with Chandra at an angular distance of ∼2.9 arcsec to XTE J1752−223 and at a position angle consistent with that of the radio jets previously observed from the BHT. We discuss the possibility that we detected X-ray emission associated with a jet from XTE J1752−223.
We present the first results of coordinated multiwavelength observations of the Galactic black hole GX 339-4 in a canonical low/hard state, obtained during its 2004 outburst. XMM-Newton observed the ...source for two revolutions, or approximately 280 ks; RXTE monitored the source throughout this long stare. The resulting data offer the best view yet obtained of the inner accretion flow geometry in the low/hard state, which is thought to be analogous to the geometry in low-luminosity active galactic nuclei. The XMM-Newton spectra clearly reveal the presence of a cool accretion disk component and a relativistic Fe K emission line. The results of fits made to both components strongly suggest that a standard thin disk remains at or near to the innermost stable circular orbit, at least in bright phases of the low/hard state. These findings indicate that potential links between the inner disk radius and the onset of a steady compact jet, and the paradigm of a radially recessed disk in the low/hard state, do not hold universally. The results of our observations can best be explained if a standard thin accretion disk fuels a corona that is closely related to, or consistent with, the base of a compact jet. In a brief examination of archival data, we show that Cygnus X-1 supports this picture of the low/hard state. We discuss our results within the context of disk-jet connections and prevailing models for accretion onto black holes.
The gap between supply and demand in kidney transplantation has led to increased use of marginal kidneys; however, kidneys with acute kidney injury are often declined/discarded. To determine whether ...this policy is justified, we analyzed outcomes of donor kidneys with acute kidney injury (AKI) in a large UK cohort. A retrospective analysis of the UK Transplant Registry evaluated deceased donors between 2003 and 2013. Donors were classified as no AKI, or AKI stage 1–3 according to Acute Kidney Injury Network (AKIN) criteria. Relationship of AKI with delayed graft function/primary nonfunction (DGF/PNF), estimated glomerular filtration rate (eGFR), and graft‐survival at 90 days and 1 year was analyzed. There were 11 219 kidneys (1869 17% with AKI) included. Graft failure at 1 year is greater for donors with AKI than for those without (graft survival 89% vs. 91%, p = 0.02; odds ratio (OR) 1.20 95% confidence interval (CI): 1.03–1.41). DGF rates increase with donor AKI stage (p < 0.005), and PNF rates are significantly higher for AKIN stage 3 kidneys (9% vs. 4%, p = 0.04) Analysis of association between AKI and recipient eGFR suggests a risk of inferior eGFR with AKI versus no AKI (p < 0.005; OR 1.25 95% CI: 1.08–1.31). We report a small reduction in 1‐year graft‐survival of kidneys from donors with AKI. We conclude that AKI stage 1 or 2 kidneys should be used; however, caution is advised for AKI stage 3 donors.
This analysis of the UK transplant registry investigates the use of kidneys from deceased donors with acute kidney injury and analyzes the outcomes of transplanted kidneys with injury.
In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and ...total immunosuppression while maintaining efficacy. We performed a randomized controlled, open‐label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL). Primary outcomes were renal fibrosis and inflammation. Secondary outcomes were estimated glomerular filtration rate (eGFR) and incidence of rejection at 24 months. The P/MPS arm was prematurely halted. The trial continued with P/CsA (N = 89) and P/EVL (N = 96). Interstitial fibrosis and inflammation were significantly decreased and the eGFR was significantly higher in the P/EVL arm. Cumulative rejection rates were 13% (P/EVL) and 19% (P/CsA), (p = 0.08). A post hoc analysis of HLA and donor‐specific antibodies at 1 year after transplantation revealed no differences. An individualized immunosuppressive strategy of early CNI elimination to dual therapy with everolimus was associated with decreased allograft fibrosis, preserved allograft function, and good efficacy, but also with more serious adverse events and discontinuation. This can be a valuable alternative regimen in patients suffering from CNI toxicity.
This randomized trial in renal transplant recipients shows that with tight monitoring of drug levels, a triple calcineurin inhibitor–containing drug maintenance regimen can be tapered to a double calcineurin‐free drug regimen, and that this regimen is associated with better renal function and less interstitial fibrosis and inflammation.
Abstract
The role of metabolite-responsive riboswitches in regulating gene expression in bacteria is well known and makes them useful systems for the study of RNA-small molecule interactions. Here, ...we study the PreQ
1
riboswitch system, assessing sixteen diverse PreQ
1
-derived probes for their ability to selectively modify the class-I PreQ
1
riboswitch aptamer covalently. For the most active probe (
11
), a diazirine-based photocrosslinking analog of PreQ
1
, X-ray crystallography and gel-based competition assays demonstrated the mode of binding of the ligand to the aptamer, and functional assays demonstrated that the probe retains activity against the full riboswitch. Transcriptome-wide mapping using Chem-CLIP revealed a highly selective interaction between the bacterial aptamer and the probe. In addition, a small number of RNA targets in endogenous human transcripts were found to bind specifically to
11
, providing evidence for candidate PreQ
1
aptamers in human RNA. This work demonstrates a stark influence of linker chemistry and structure on the ability of molecules to crosslink RNA, reveals that the PreQ
1
aptamer/ligand pair are broadly useful for chemical biology applications, and provides insights into how PreQ
1
, which is similar in structure to guanine, interacts with human RNAs.
PDF
