Isolation of 10 cyclosporine metabolites from human bile

Ten metabolites of cyclosporine were isolated from the ethyl ether extract of bile from four liver transplant patients receiving cyclosporine. Two of the metabolites were unique and previously unidentified. Liquid-liquid partitioning into diethyl ether with subsequent defatting with n-hexane was used for the initial extraction form bile. Separation of the individual metabolites (A-J) was performed using a Sephadex LH-20 column and a gradient high performance liquid chromatographic method. The molecular weights of the isolated metabolites were determined by fast atom bombardment/mass spectrometry. Gas chromatography with mass spectrometic amino acid analysis was also used to identify the amino acid composition and the hydroxylation position of metabolites A, B, C, D, and G. Proton nuclear magnetic resonance spectra were utilized to disinguish the chemical shifts of N-CH3 singlets and NH doublets of metabolites A, B, C, and D. Metabolites A, E, F, H, I, and J were reported previously in human urine and animal bile. Metabolites C and D are dihydroxylated compounds which cannot be clearly described as previously isolated compounds. Metabolites B and G are novel metabolites with a mass fragment which corresponded to a loss of 131 Da from the protonated molecular ion (MH+) in the fast atom bombardment/mass spectrometry, suggesting that the double bond in amino acid 1 has been modified. Metabolites B and G were primarily isolated from the bile of one of the liver transplant patients which contained abnormally high concentrations of these two metabolites. The method described is an efficient procedure for isolating milligram quantities of the major metabolites with greater than 95% purity

Chandra and Swift X-ray Observations of the X-ray Pulsar SMC X-2 During the Outburst of 2015

We report the Chandra/HRC-S and Swift/XRT observations for the 2015 outburst of the high-mass X-ray binary pulsar in the Small Magellanic Cloud, SMC X-2. While previous studies suggested that either an O star or a Be star in the field is the high-mass companion of SMC X-2, our Chandra/HRC-S image unambiguously confirms the O-type star as the true optical counterpart. Using the Swift/XRT observations, we extracted accurate orbital parameters of the pulsar binary through a time of arrivals analysis. In addition, there were two X-ray dips near the inferior conjunction, which are possibly caused by eclipses or an ionized high-density shadow wind near the companion’s surface. Finally, we propose that an outflow driven by the radiation pressure from day ∼10 played an important role in the X-ray/optical evolution of the outburst.postprin

Abdominal Surgical Emergencies at Tikur Anbessa Specialized Hospital in Ethiopia; A Shifting Paradigm

Background: Developing nations in Africa may be experiencing changing demographics for abdominal surgical emergencies. In the past, intestinal obstruction has been the major diagnosis, but this may be changing.123 This study analyzed the causes and outcomes for abdominal surgicalemergencies (ASE) in Tikur Anbessa Specialty Hospital (TASH) in Addis Ababa, Ethiopia.Methods: TASH is a tertiary medical center and teaching hospital. This is retrospective study included patients treated for ASE from July 1, 2010 to June 30, 2012. Information was collected in de-identified manner for analysis from the operating room logbook and from chart review. We analyzed demographics, clinical presentation and outcomes of emergency surgery in these patents using SAS 9.2 software. Univariant analysis was performed. P value < 0.05 was considered significant.Results: A total of 530 patients presented with ASE, representing 18.6% of all surgical emergencies. Of these, 328 charts were available for review. 237 (72.3%) were males and the mean age was 36 years. Appendicitis (simple and complicated combined) were the most common cause of ASE accounting for 92 (28.0%). Bowel obstruction and penetrating trauma were present in 17% and 13% of the time respectively. The Overall Morbidity and mortality rates were 30% and 18% respectively. Wound infection andPneumonia were the two most common post operative complications  accounting for 25% and 12% respectively. A total of 61 patients (18.6%) died following ASE. Septic complications accounted for over 50% of the death. Mortality was significantly higher in patients with age >60 years (p<0.0001) and in those who developed post operative complications. (p< 0.0001)Conclusion: The causes for ASE at TASH in Ethiopia have changed with appendicitis being the most common. This study shows a higher morbidity and mortality rates when compared to previous reports. Further study is required to understand better specific interventions needed to reduce thishigh mortality due to sepsis

Swift Detection of a 65 Day X-Ray Period from the Ultraluminous Pulsar NGC 7793 P13

NGC 7793 P13 is an ultraluminous X-ray source harboring an accreting pulsar. We report on the detection of a ~65 day period X-ray modulation with Swift observations in this system. The modulation period found in the X-ray band is P = 65.05 ± 0.10 days and the profile is asymmetric with a fast rise and a slower decay. On the other hand, the u-band light curve collected by Swift UVOT confirmed an optical modulation with a period of P = 64.24 ± 0.13 days. We explored the phase evolution of the X-ray and optical periodicities and propose two solutions. A superorbital modulation with a period of ~2700–4700 days probably caused by the precession of a warped accretion disk is necessary to interpret the phase drift of the optical data. We further discuss the implication if this ~65 day periodicity is caused by the superorbital modulation. Estimated from the relationship between the spin-orbital and orbital-superorbital periods of known disk-fed high-mass X-ray binaries, the orbital period of P13 is roughly estimated as 3–7 days. In this case, an unknown mechanism with a much longer timescale is needed to interpret the phase drift. Further studies on the stability of these two periodicities with a long-term monitoring could help us to probe their physical origins.postprin

Evolution of Spin, Orbital, and Superorbital Modulations of 4U 0114+650

We report a systematic analysis of the spin, orbital, and superorbital modulations of 4U 0114+650, a high-mass X-ray binary that consists of one of the slowest spinning neutron stars. Using the dynamic power spectrum, we found that the spin period varied dramatically and is anticorrelated with the long-term X-ray flux variation that can be observed using the Rossi X-ray Timing Explorer ASM, Swift BAT, and the Monitor of All-sky X-ray Image. The spin-up rate over the entire data set is consistent with previously reported values; however, the local spin-up rate is considerably higher. The corresponding local spin-up timescale is comparable to the local spin-up rate of OAO 1657−415, indicating that 4U 0114+650 could also have a transient disk. Moreover, the spin period evolution shows two ∼1000-day spin-down/random-walk epochs that appeared together with depressions of the superorbital modulation amplitude. This implies that the superorbital modulation was closely related to the presence of the accretion disk, which is not favored in the spin-down/random-walk epochs because the accretion is dominated by the direct wind accretion. The orbital period is stable during the entire time span; however, the orbital profile significantly changes with time. We found that the depth of the dip near the inferior conjunction of the companion is highly variable, which disfavors the eclipsing scenario. Moreover, the dip was less obvious during the spin-down/random-walk epochs, indicating its correlation with the accretion disk. Further monitoring in both X-ray and optical bands could reveal the establishment of the accretion disk in this system.postprin

First Nonperturbative Test of a Relativistic Heavy Quark Action in Quenched Lattice QCD

We perform a numerical test of a relativistic heavy quark(RHQ) action, recently proposed by Tsukuba group, in quenched lattice QCD at $a\simeq 0.1$ fm. With the use of the improvement parameters previously determined at one-loop level for the RHQ action, we investigate a restoration of rotational symmetry for heavy-heavy and heavy-light meson systems around the charm quark mass. We focused on two quantities, the meson dispersion relation and the pseudo-scalar meson decay constants. It is shown that the RHQ action significantly reduces the discretization errors due to the charm quark mass. We also calculate the S-state hyperfine splittings for the charmonium and charmed-strange mesons and the $D_s$ meson decay constant. The remaining discretization errors in the physical quantities are discussed.Comment: 21 pages, 16 figures. A reference and a comment added, a major modification in appendix, several minor changes in the abstract and the main text. Errors in affiliation are corrected. Version appeared in JHE

Construction of endophenotypes for complex diseases in the presence of heterogeneity

Endophenotypes such as behavior disorders have been increasingly adopted in genetic studies for complex traits. For efficient gene mapping, it is essential that an endophenotype is associated with the disease of interest and is inheritable or co-segregating within families. In this study, we proposed a strategy to construct endophenotypes to analyze the Genetic Analysis Workshop 14 simulated dataset. Initially, generalized estimating equation models were employed to identify phenotypes that were correlated to the disease (affected status) in combination with the family structures in data. Endophenotypes were then constructed with consideration of heterogeneity as functions of the identified phenotypes. Genome scans on the constructed endophenotypes were carried out using family-based association analysis. For comparison, genome scans were also performed with the original affected status. The family-based association analysis using the endophenotypes correctly identified the same susceptible gene in about 80 of the 100 replicates

Faint young Sun paradox remains

The Sun was fainter when the Earth was young, but the climate was generally at least as warm as today; this is known as the `faint young Sun paradox'. Rosing et al. [1] claim that the paradox can be resolved by making the early Earth's clouds and surface less reflective. We show that, even with the strongest plausible assumptions, reducing cloud and surface albedos falls short by a factor of two of resolving the paradox. A temperate Archean climate cannot be reconciled with the low level of CO2 suggested by Rosing et al. [1]; a stronger greenhouse effect is needed.Comment: 3 pages, no figures. In press in Nature. v2 corrects typo in author list in original submissio

Small Hairy Black Holes in Global AdS Spacetime

We study small charged black holes in global AdS spacetime in the presence of a charged massless minimally coupled scalar field. In a certain parameter range these black holes suffer from well known superradiant instabilities. We demonstrate that the end point of the resultant tachyon condensation process is a hairy black hole which we construct analytically in a perturbative expansion in the black hole radius. At leading order our solution is a small undeformed RNAdS black hole immersed into a charged scalar condensate that fills the AdS `box'. These hairy black hole solutions appear in a two parameter family labelled by their mass and charge. Their mass is bounded from below by a function of their charge; at the lower bound a hairy black hole reduces to a regular horizon free soliton which can also be thought of as a nonlinear Bose condensate. We compute the microcanonical phase diagram of our system at small mass, and demonstrate that it exhibits a second order `phase transition' between the RNAdS black hole and the hairy black hole phases.Comment: 68+1 pages, 18 figures, JHEP format. v2 : small typos corrected and a reference adde