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

Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain

<p>Abstract</p> <p>Background</p> <p>Mechanisms driving cancer-induced bone pain are poorly understood. A central factor implicated to be a key player in the process of tumorigenesis, osteoclastogenesis and nociception is p38 MAPK. We determined the role of p38 MAPK in a mouse model of breast cancer induced bone pain in which mixed osteolytic and osteoblastic remodeling occurs.</p> <p>Results</p> <p>In cancer-treated mice, acute as well as chronic inhibition of p38 MAPK with SB203580 blocked flinching and guarding behaviors in a dose-dependent manner whereas no effect on thresholds to tactile stimuli was observed. Radiographic analyses of bones demonstrated that chronic inhibition of p38 MAPK reduced bone loss and incidence of spontaneous fracture in cancer-treated mice. Histological analysis of bones collected from mice treated with the p38 MAPK inhibitor showed complete absence of osteoblastic growth in the intramedullary space as well as significantly reduced tumor burden.</p> <p>Conclusions</p> <p>Blockade of non-evoked pain behaviors but not hypersensitivity suggests differences in the underlying mechanisms of specific components of the pain syndrome and a possibility to individualize aspects of pain management. While it is not known whether the role of p38 MAPK signaling can be expanded to other cancers, the data suggest a need for understanding molecular mechanisms and cellular events that initiate and maintain cancer-induced bone pain for effective management for both ongoing pain as well as breakthrough pain.</p

The corona of the broad-line radio galaxy 3C 390.3

We present the results from a joint Suzaku/NuSTAR broad-band spectral analysis of 3C 390.3. The high quality data enables us to clearly separate the primary continuum from the reprocessed components allowing us to detect a high energy spectral cut-off ($E_\text{cut}=117_{-14}^{+18}$ keV), and to place constraints on the Comptonization parameters of the primary continuum for the first time. The hard over soft compactness is 69$_{-24}^{+124}$ and the optical depth 4.1$_{-3.6}^{+0.5}$, this leads to an electron temperature of $30_{-8}^{+32}$ keV. Expanding our study of the Comptonization spectrum to the optical/UV by studying the simultaneous Swift-UVOT data, we find indications that the compactness of the corona allows only a small fraction of the total UV/optical flux to be Comptonized. Our analysis of the reprocessed emission show that 3C 390.3 only has a small amount of reflection (R~0.3), and of that the vast majority is from distant neutral matter. However we also discover a soft X-ray excess in the source, which can be described by a weak ionized reflection component from the inner parts of the accretion disk. In addition to the backscattered emission, we also detect the highly ionized iron emission lines Fe XXV and Fe XXVI

Dental Microwear and Diet of the Plio-Pleistocene Hominin Paranthropus boisei

The Plio-Pleistocene hominin Paranthropus boisei had enormous, flat, thickly enameled cheek teeth, a robust cranium and mandible, and inferred massive, powerful chewing muscles. This specialized morphology, which earned P. boisei the nickname “Nutcracker Man”, suggests that this hominin could have consumed very mechanically challenging foods. It has been recently argued, however, that specialized hominin morphology may indicate adaptations for the consumption of occasional fallback foods rather than preferred resources. Dental microwear offers a potential means by which to test this hypothesis in that it reflects actual use rather than genetic adaptation. High microwear surface texture complexity and anisotropy in extant primates can be associated with the consumption of exceptionally hard and tough foods respectively. Here we present the first quantitative analysis of dental microwear for P. boisei. Seven specimens examined preserved unobscured antemortem molar microwear. These all show relatively low complexity and anisotropy values. This suggests that none of the individuals consumed especially hard or tough foods in the days before they died. The apparent discrepancy between microwear and functional anatomy is consistent with the idea that P. boisei presents a hominin example of Liem's Paradox, wherein a highly derived morphology need not reflect a specialized diet

The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

Global Taxonomic Diversity of Anomodonts (Tetrapoda, Therapsida) and the Terrestrial Rock Record Across the Permian-Triassic Boundary

The end-Permian biotic crisis (∼252.5 Ma) represents the most severe extinction event in Earth's history. This paper investigates diversity patterns in Anomodontia, an extinct group of therapsid synapsids (‘mammal-like reptiles’), through time and in particular across this event. As herbivores and the dominant terrestrial tetrapods of their time, anomodonts play a central role in assessing the impact of the end-Permian extinction on terrestrial ecosystems. Taxonomic diversity analysis reveals that anomodonts experienced three distinct phases of diversification interrupted by the same number of extinctions, i.e. an end-Guadalupian, an end-Permian, and a mid-Triassic extinction. A positive correlation between the number of taxa and the number of formations per time interval shows that anomodont diversity is biased by the Permian-Triassic terrestrial rock record. Normalized diversity curves indicate that anomodont richness continuously declines from the Middle Permian to the Late Triassic, but also reveals all three extinction events. Taxonomic rates (origination and extinction) indicate that the end-Guadalupian and end-Permian extinctions were driven by increased rates of extinction as well as low origination rates. However, this pattern is not evident at the final decline of anomodont diversity during the Middle Triassic. Therefore, it remains unclear whether the Middle Triassic extinction represents a gradual or abrupt event that is unique to anomodonts or more common among terrestrial tetrapods. The end-Permian extinction represents the most distinct event in terms of decline in anomodont richness and turnover rates

Community Justice and Public Safety: Assessing Criminal Justice Policy Through the Lens of the Social Contract

A reconceptualization of the idea of “community justice” is framed in the logic of the social contract and emphasizes the responsibility of the justice system for the provision of public safety. First, we illustrate the ways in which the criminal justice system has hindered the efforts of community residents to participate in the production of public safety by disrupting informal social networks. Then we turn to an examination of the compositional dynamics of California prison populations over time to demonstrate that the American justice system has failed to meet their obligations to provide public safety by incapacitating dangerous offenders. We argue that these policy failures represent a breach of the social contract and advocate for more effective collaboration between communities and the formal criminal justice system so that all parties can fulfill their obligations under the contract

Mathematical Modeling of Malaria Infection with Innate and Adaptive Immunity in Individuals and Agent-Based Communities

Background: Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns). Methodology/Principal Findings: We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT) studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB) communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities. Conclusions/Significance: Our approach represents a novel, convenient and versatile method to model Plasmodiu

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-

Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076]

BACKGROUND: Bronchiolitis is the most common cause of lower respiratory tract illness in infancy, and hospital admission rates appear to be increasing in Canada and the United States. Inhaled beta agonists offer only modest short-term improvement. Trials of racemic epinephrine have shown conflicting results. We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress, was safe, and shortened length of stay. METHODS: The study was a randomized, double-blind controlled trial of aerosolized racemic epinephrine compared to salbutamol every one to 4 hours in previously well children aged 6 weeks to ≤ 2 years of age hospitalized with bronchiolitis. The primary outcome was symptom improvement as measured by the Respiratory Distress Assessment Instrument (RDAI); secondary outcomes were length of stay in hospital, adverse events, and report of symptoms by structured parental telephone interview one week after discharge. RESULTS: 62 children with a mean age of 6.4 months were enrolled; 80% of children had Respiratory Syncytial Virus (RSV). Racemic epinephrine resulted in significant improvement in wheezing and the total RDAI score on day 2 and over the entire stay (p < 0.05). The mean LOS in the epinephrine arm was 2.6 days (95% CI 2, 3.2) v. 3.4 days in those in the salbutamol group (95% CI 2.6, 4.2) (p > 0.05). Adverse events were not significantly different in the two arms. At one week post-discharge, over half of parents reported that their child still had a respiratory symptom and 40% had less than normal feeding. CONCLUSION: Racemic epinephrine relieves respiratory distress in hospitalized infants with bronchiolitis and is safe but does not abbreviate hospital stay. Morbidity associated with bronchiolitis as identified by parents persists for at least one week after hospital discharge in most infants