POWERFUL, ROTATING DISK WINDS from STELLAR-MASS BLACK HOLES

We present an analysis of ionized X-ray disk winds observed in the Fe K band of four stellar-mass black holes observed with Chandra, including 4U 1630-47, GRO J1655-40, H 1743-322, and GRS 1915+105. High-resolution photoionization grids were generated in order to model the data. Third-order gratings spectra were used to resolve complex absorption profiles into atomic effects and multiple velocity components. The Fe XXV line is found to be shaped by contributions from the intercombination line (in absorption), and the Fe XXVI line is detected as a spin-orbit doublet. The data require 2-3 absorption zones, depending on the source. The fastest components have velocities approaching or exceeding 0.01c, increasing mass outflow rates and wind kinetic power by orders of magnitude over prior single-zone models. The first-order spectra require re-emission from the wind, broadened by a degree that is loosely consistent with Keplerian orbital velocities at the photoionization radius. This suggests that disk winds are rotating with the orbital velocity of the underlying disk, and provides a new means of estimating launching radii -- crucial to understanding wind driving mechanisms. Some aspects of the wind velocities and radii correspond well to the broad-line region (BLR) in active galactic nuclei, suggesting a physical connection. We discuss these results in terms of prevalent models for disk wind production and disk accretion itself, and implications for massive black holes in active galactic nuclei

THE ACCRETION DISK WIND IN THE BLACK HOLE GRS 1915+105

© 2016. The American Astronomical Society. All rights reserved. We report on a 120 ks Chandra/HETG spectrum of the black hole GRS 1915+105. The observation was made during an extended and bright soft state in 2015 June. An extremely rich disk wind absorption spectrum is detected, similar to that observed at lower sensitivity in 2007. The very high resolution of the third-order spectrum reveals four components to the disk wind in the Fe K band alone; the fastest has a blueshift of v = 0.03c. Broadened re-emission from the wind is also detected in the first-order spectrum, giving rise to clear accretion disk P Cygni profiles. Dynamical modeling of the re-emission spectrum gives wind launching radii of r ≃ 102-4 GM/c2. Wind density values of n ≃ 1013-16 cm-3 are then required by the ionization parameter formalism. The small launching radii, high density values, and inferred high mass outflow rates signal a role for magnetic driving. With simple, reasonable assumptions, the wind properties constrain the magnitude of the emergent magnetic field to be B ≃ 103-4 G if the wind is driven via magnetohydrodynamic (MHD) pressure from within the disk and B ≃ 104-5 G if the wind is driven by magnetocentrifugal acceleration. The MHD estimates are below upper limits predicted by the canonical α-disk model. We discuss these results in terms of fundamental disk physics and black hole accretion modes

Epigenetic Inactivation of the miR-124-1 in Haematological Malignancies

miR-124-1 is a tumour suppressor microRNA (miR). Epigenetic deregulation of miRs is implicated in carcinogenesis. Promoter DNA methylation and histone modification of miR-124-1 was studied in 5 normal marrow controls, 4 lymphoma, 8 multiple myeloma (MM) cell lines, 230 diagnostic primary samples of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), MM, and non-Hodgkin's lymphoma (NHL), and 53 MM samples at stable disease or relapse. Promoter of miR-124-1 was unmethylated in normal controls but homozygously methylated in 4 of 4 lymphoma and 4 of 8 myeloma cell lines. Treatment of 5-Aza-2′-deoxycytidine led to miR-124-1 demethylation and re-expression of mature miR-124, which also associated with emergence of euchromatic trimethyl H3K4 and consequent downregulation of CDK6 in myeloma cells harboring homozygous miR-124-1 methylation. In primary samples at diagnosis, miR-124-1 methylation was absent in CML but detected in 2% each of MM at diagnosis and relapse/progression, 5% ALL, 15% AML, 14% CLL and 58.1% of NHL (p<0.001). Amongst lymphoid malignancies, miR-124-1 was preferentially methylated in NHL than MM, CLL or ALL. In primary lymphoma samples, miR-124-1 was preferentially hypermethylated in B- or NK/T-cell lymphomas and associated with reduced miR-124 expression. In conclusion, miR-124-1 was hypermethylated in a tumour-specific manner, with a heterochromatic histone configuration. Hypomethylation led to partial restoration of euchromatic histone code and miR re-expression. Infrequent miR-124-1 methylation detected in diagnostic and relapse MM samples showed an unimportant role in MM pathogenesis, despite frequent methylation found in cell lines. Amongst haematological cancers, miR-124-1 was more frequently hypermethylated in NHL, and hence warrants further study

What factors explain the number of physical therapy treatment sessions in patients referred with low back pain; a multilevel analysis

BACKGROUND: It is well-known that the number of physical therapy treatment sessions varies over treatment episodes. Information is lacking, however, on the source and explanation of the variation. The purposes of the current study are: 1) to determine how the variance in the number of physical therapy treatment sessions in patients with non-specific low back pain (LBP) in the Netherlands is distributed over patient level, therapist level and practice level; and 2) to determine the factors that explain the variance. METHODS: Data were used from a national registration network on physical therapy. Our database contained information on 1,733 patients referred with LBP, treated by 97 therapists working in 41 practices. The variation in the number of treatment sessions was investigated by means of multilevel regression analyses. RESULTS: Eighty-eight per cent of the variation in the number of treatment sessions for patients with LBP is located at patient level and seven per cent is located at practice level. It was possible to explain thirteen per cent of all variance. The duration of the complaint, prior therapy, and the patients' age and gender in particular are related to the number of physical therapy treatment sessions. CONCLUSION: Our results suggest that the number of physical therapy treatment sessions in patients with LBP mainly depends on patient characteristics. More variation needs to be explained, however, to improve the transparency of care. Future research should examine the contribution of psychosocial factors, baseline disability, and the ability to learn motor behavior as possible factors in the variation in treatment sessions

Genes Involved in Oxidative Stress Pathways Are Differentially Expressed in Circulating Mononuclear Cells Derived From Obese Insulin-Resistant and Lean Insulin-Sensitive Individuals Following a Single Mixed-Meal Challenge.

Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition. Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges. Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group. Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases

DISK–WIND CONNECTION DURING THE HEARTBEATS OF GRS 1915+105

Disk and wind signatures are seen in the soft state of Galactic black holes, while the jet is seen in the hard state. Here we study the disk–wind connection in the ρ class of variability in GRS 1915+105 using a joint NuSTAR–Chandra observation. The source shows 50 s limit cycle oscillations. By including new information provided by the reflection spectrum and using phase-resolved spectroscopy, we find that the change in the inner disk inferred from the blackbody emission is not matched by reflection measurements. The latter is almost constant, independent of the continuum model. The two radii are comparable only if the disk temperature color correction factor changes, an effect that could be due to the changing opacity of the disk caused by changes in metal abundances. The disk inclination is similar to that inferred from the jet axis, and oscillates by ~10°. The simultaneous Chandra data show the presence of two wind components with velocities between 500 and 5000 km s⁻¹, and possibly two more with velocities reaching 20,000 km s⁻¹ (~0.06 c). The column densities are ~5 × 10²² cm⁻². An upper limit to the wind response time of 2 s is measured, implying a launch radius of <6 × 10¹° cm. The changes in wind velocity and absorbed flux require the geometry of the wind to change during the oscillations, constraining the wind to be launched from a distance of 290–1300 r _g from the black hole. Both data sets support fundamental model predictions in which a bulge originates in the inner disk and moves outward as the instability progresses.This work made use of data from the NuSTAR mission, a project led by the California Institute of Technology, managed by the Jet Propulsion Laboratory, and funded by the National Aeronautics and Space Administration. This work is also based on observations made by the Chandra X-ray Observatory

The changing carbon cycle of the coastal ocean

The carbon cycle of the coastal ocean is a dynamic component of the global carbon budget. But the diverse sources and sinks of carbon and their complex interactions in these waters remain poorly understood. Here we discuss the sources, exchanges and fates of carbon in the coastal ocean and how anthropogenic activities have altered the carbon cycle. Recent evidence suggests that the coastal ocean may have become a net sink for atmospheric carbon dioxide during post-industrial times. Continued human pressures in coastal zones will probably have an important impact on the future evolution of the coastal ocean's carbon budget

Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation.

INTRODUCTION AND OBJECTIVE: Heredity of type 2 diabetes mellitus (T2DM) is associated with greater risk for developing T2DM. Thus, individuals who have a first-degree relative with T2DM (FDRT) provide a natural model to study factors of susceptibility towards development of T2DM, which are poorly understood. Emerging key players in T2DM pathophysiology such as adverse oxidative stress and inflammatory responses could be among possible mechanisms that predispose FDRTs to develop T2DM. Here, we aimed to examine the role of oxidative stress and inflammatory responses as mediators of this excess risk by studying dynamic postprandial responses in FDRTs. RESEARCH DESIGN AND METHODS: In this open-label case-control study, we recruited normoglycemic men with (n=9) or without (n=9) a family history of T2DM. We assessed plasma glucose, insulin, lipid profile, cytokines and F2-isoprostanes, expression levels of oxidative and inflammatory genes/proteins in circulating mononuclear cells (MNC), myotubes and adipocytes at baseline (fasting state), and after consumption of a carbohydrate-rich liquid meal or insulin stimulation. RESULTS: Postprandial glucose and insulin responses were not different between groups. Expression of oxidant transcription factor NRF2 protein (p<0.05 for myotubes) and gene (pgroup=0.002, ptime×group=0.016), along with its target genes TXNRD1 (pgroup=0.004, ptime×group=0.007), GPX3 (pgroup=0.011, ptime×group=0.019) and SOD-1 (pgroup=0.046 and ptime×group=0.191) was upregulated in FDRT-derived MNC after meal ingestion or insulin stimulation. Synergistically, expression of target genes of inflammatory transcription factor nuclear factor kappa B such as tumor necrosis factor alpha (pgroup=0.001, ptime×group=0.007) was greater in FDRT-derived MNC than in non-FDRT-derived MNC after meal ingestion or insulin stimulation. CONCLUSIONS: Our findings shed light on how heredity of T2DM confers increased susceptibility to oxidative stress and inflammation. This could provide early insights into the underlying mechanisms and future risk of FDRTs for developing T2DM and its associated complications

STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al