Equation of State in Relativistic Magnetohydrodynamics: variable versus constant adiabatic index

The role of the equation of state for a perfectly conducting, relativistic magnetized fluid is the main subject of this work. The ideal constant $\Gamma$-law equation of state, commonly adopted in a wide range of astrophysical applications, is compared with a more realistic equation of state that better approximates the single-specie relativistic gas. The paper focus on three different topics. First, the influence of a more realistic equation of state on the propagation of fast magneto-sonic shocks is investigated. This calls into question the validity of the constant $\Gamma$-law equation of state in problems where the temperature of the gas substantially changes across hydromagnetic waves. Second, we present a new inversion scheme to recover primitive variables (such as rest-mass density and pressure) from conservative ones that allows for a general equation of state and avoids catastrophic numerical cancellations in the non-relativistic and ultrarelativistic limits. Finally, selected numerical tests of astrophysical relevance (including magnetized accretion flows around Kerr black holes) are compared using different equations of state. Our main conclusion is that the choice of a realistic equation of state can considerably bear upon the solution when transitions from cold to hot gas (or viceversa) are present. Under these circumstances, a polytropic equation of state can significantly endanger the solution.Comment: 14 pages, 14 figure

Three-Dimensional Simulations of Magnetized Thin Accretion Disks around Black Holes: Stress in the Plunging Region

We describe three-dimensional general relativistic magnetohydrodynamic simulations of a geometrically thin accretion disk around a non-spinning black hole. The disk has a thickness $h/r\sim0.05-0.1$ over the radial range $(2-20)GM/c^2$. In steady state, the specific angular momentum profile of the inflowing magnetized gas deviates by less than 2% from that of the standard thin disk model of Novikov & Thorne (1973). Also, the magnetic torque at the radius of the innermost stable circular orbit (ISCO) is only $\sim2$ of the inward flux of angular momentum at this radius. Both results indicate that magnetic coupling across the ISCO is relatively unimportant for geometrically thin disks.Comment: 4 pages, 4 figures, ApJL accepte

Measuring Black Hole Spin by the Continuum-Fitting Method: Effect of Deviations from the Novikov-Thorne Disc Model

The X-ray spectra of accretion discs of eight stellar-mass black holes have been analyzed to date using the thermal continuum fitting method, and the spectral fits have been used to estimate the spin parameters of the black holes. However, the underlying model used in this method of estimating spin is the general relativistic thin-disc model of Novikov & Thorne, which is only valid for razor-thin discs. We therefore expect errors in the measured values of spin due to inadequacies in the theoretical model. We investigate this issue by computing spectra of numerically calculated models of thin accretion discs around black holes, obtained via three-dimensional general relativistic magnetohydrodynamic (GRMHD) simulations. We apply the continuum fitting method to these computed spectra to estimate the black hole spins and check how closely the values match the actual spin used in the GRMHD simulations. We find that the error in the dimensionless spin parameter is up to about 0.2 for a non-spinning black hole, depending on the inclination. For black holes with spins of 0.7, 0.9 and 0.98, the errors are up to about 0.1, 0.03 and 0.01 respectively. These errors are comparable to or smaller than those arising from current levels of observational uncertainty. Furthermore, we estimate that the GRMHD simulated discs from which these error estimates are obtained correspond to effective disc luminosities of about 0.4-0.7 Eddington, and that the errors will be smaller for discs with luminosities of 0.3 Eddington or less, which are used in the continuum-fitting method. We thus conclude that use of the Novikov-Thorne thin-disc model does not presently limit the accuracy of the continuum-fitting method of measuring black hole spin.Comment: 13 pages, 7 figures, accepted for publication in MNRAS. v2: fixed typo in author name, updated acknowledgment

Using action inquiry to address critical challenges

Action research involves researchers and practitioners in collaborative projects and provides a means of integrating evaluation into the reform process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49310/1/180_ftp.pd

Partnering for Quail in South Carolina: A Cooperative Approach Making a Difference

The National Bobwhite Conservation Initiative (NBCI) identified 15 national quail focal areas throughout the distribution of the northern bobwhite (Colinus virginianus) in June 2016. The first NBCI Focal Area on U.S. Forest Service System land emerged from the existing 16,200-hectare Indian Creek Woodland and Savanna Restoration Initiative (ICWSRI). The ICWSRI is an ongoing collaborative project involving partners from 10 agencies and organizations in the Piedmont of South Carolina. Cooperation among federal and state agencies, non-governmental organizations (NGO), and private landowners, combined with assistance programs such as the Environmental Quality Incentives Program (EQIP) have currently resulted in 2,547 hectares (1,600 hectares on private land and 947 hectares on public land) of improved habitat for wildlife species associated with pine woodlands and savannas. Data obtained through the Breeding Bird Survey, spring whistle counts, and fall covey counts suggest a correlation between woodland and savanna restoration and avian response across the ICWSRI area. Fall covey count minimum population estimates (birds/ha) ranged from 1/38 in 2008 to 1/7 in 2016. Spring whistle count population density estimates (birds/ha) ranged from 1/37 in 2009 to 1/6 in 2012. Although monitoring suggests an initial increase in bobwhite densities across the project area, it is imperative to continue involving existing and additional partners to increase habitat availability, connectivity, and quality for bobwhite and associated species. Collaborative efforts and partnerships across ownership boundaries are necessary to increase bobwhite populations on a landscape scale. The Indian Creek project has effectively involved efforts from federal, state, NGO, and private partners to restore and improve bobwhite habitat and may serve as an example for other areas where incorporating a cooperative approach could positively influence bobwhite populations

Quaternary structure of the specific p53-DNA complex reveals the mechanism of p53 mutant dominance

The p53 tumour suppressor is a transcriptional activator that controls cell fate in response to various stresses. p53 can initiate cell cycle arrest, senescence and/or apoptosis via transactivation of p53 target genes, thus preventing cancer onset. Mutations that impair p53 usually occur in the core domain and negate the p53 sequence-specific DNA binding. Moreover, these mutations exhibit a dominant negative effect on the remaining wild-type p53. Here, we report the cryo electron microscopy structure of the full-length p53 tetramer bound to a DNA-encoding transcription factor response element (RE) at a resolution of 21 Å. While two core domains from both dimers of the p53 tetramer interact with DNA within the complex, the other two core domains remain available for binding another DNA site. This finding helps to explain the dominant negative effect of p53 mutants based on the fact that p53 dimers are formed co-translationally before the whole tetramer assembles; therefore, a single mutant dimer would prevent the p53 tetramer from binding DNA. The structure indicates that the Achilles’ heel of p53 is in its dimer-of-dimers organization, thus the tetramer activity can be negated by mutation in only one allele followed by tumourigenesis

Simulations of magnetized discs around black holes: Effects of black hole spin, disc thickness and magnetic field geometry

The standard general relativistic model of a razor-thin accretion disc around a black hole, developed by Novikov & Thorne (NT) in 1973, assumes the shear stress vanishes at theradius of the innermost stable circular orbit (ISCO) and that, outside the ISCO, the shear stress is produced by an effective turbulent viscosity. However, astrophysical accretion discs are not razor thin; it is uncertain whether the shear stress necessarily vanishes at the ISCO, and the magnetic field, which is thought to drive turbulence in discs, may contain large-scale structures that do not behave like a simple local scalar viscosity. We describe 3D general relativistic magnetohydrodynamic simulations of accretion discs around black holes with a range of spin parameters, and we use the simulations to assess the validity of the NT model. Our fiducial initial magnetic field consists of multiple (alternating polarity) poloidal field loops whose shape is roughly isotropic in the disc in order to match the isotropic turbulence expected in the poloidal plane. For a thin disc with an aspect ratio |h/r|∼0.07 around a non-spinning black hole, we find a decrease in the accreted specific angular momentum of 2.9 percent relative to the NT model and an excess luminosity from inside the ISCO of 3.5 per cent. The deviations in the case of spinning black holes are also of the same order. In addition, the deviations decrease with decreasing |h/r|. We therefore conclude that magnetized thin accretion discs in X-ray binaries in the thermal/high-soft spectral state ought to be well described by the NT model, especially at luminosities below 30 per cent of Eddington where we expect a very small disc thickness |h/ r| 0.05. We use our results to determine the spin equilibrium of black hole accretion discs with a range of thicknesses and to determine how electromagnetic stresses within the ISCO depend upon black hole spin and disc thickness. We find that the electromagnetic stress and the luminosity inside the ISCO depend on the assumed initial magnetic field geometry. We consider a second geometry with field lines following density contours, which for thin discs leads to highly radially elongated magnetic field lines. This gives roughly twice larger deviations from NT for both the accreted specific angular momentum and the luminosity inside the ISCO. Lastly, we find that the disc’s corona (including any wind or jet) introduces deviations from NT in the specific angular momentum that are comparable to those contributed by the disc component, while the excess luminosity of bound gas from within the ISCO is dominated by only the disc component. Based on these indications, we suggest that differences in results between our work and other similar work are due to differences in the assumed initial magnetic field geometry as well as the inclusion of discAstronom

Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity

ABSTRACT: Tryptophan hydroxylase (TPH) carries out the 5-hydroxylation of L-Trp, which is the ratelimiting step in the synthesis of serotonin. We have prepared and characterized a stable N-terminally truncated form of human TPH that includes the catalytic domain (∆90TPH). We have also determined the conformation and distances to the catalytic non-heme iron of both L-Trp and the tetrahydrobiopterin cofactor analogue L-erythro-7,8-dihydrobiopterin (BH 2 ) bound to ∆90TPH by using 1 H NMR spectroscopy. The bound conformers of the substrate and the pterin were then docked into the modeled three-dimensional structure of TPH. The resulting ternary TPH‚BH 2 ‚L-Trp structure is very similar to that previously determined by the same methods for the complex of phenylalanine hydroxylase (PAH) with BH 2 and L-Phe [Teigen, K., et al. (1999) J. Mol. Biol. 294, 807-823]. In the model, L-Trp binds to the enzyme through interactions with Arg257, Ser336, His272, Phe318, and Phe313, and the ring of BH 2 interacts mainly with Phe241 and Glu273. The distances between the hydroxylation sites at C5 in L-Trp and C4a in the pterin, i.e., 6.1 ( 0.4 Å, and from each of these sites to the iron, i.e., 4.1 ( 0.3 and 4.4 ( 0.3 Å, respectively, are also in agreement with the formation of a transient iron-4a-peroxytetrahydropterin in the reaction, as proposed for the other hydroxylases. The different conformation of the dihydroxypropyl chain of BH 2 in PAH and TPH seems to be related to the presence of nonconserved residues, i.e., Tyr235 and Pro238 in TPH, at the cofactor binding site. Moreover, Phe313, which seems to interact with the substrate through ring stacking, corresponds to a Trp residue in both tyrosine hydroxylase and PAH (Trp326) and appears to be an important residue for influencing the substrate specificity in this family of enzymes. We show that the W326F mutation in PAH increases the relative preference for L-Trp as the substrate, while the F313W mutation in TPH increases the preference for L-Phe, possibly by a conserved active site volume effect. Tryptophan hydroxylase (TPH) 1 is a tetrahydrobiopterinand non-heme iron-dependent enzyme that hydroxylates L-tryptophan (L-Trp) to 5-hydroxy-L-Trp using (6R)-Lerythro- These tetrameric enzymes are organized in a regulatory N-terminal domain, a catalytic domain, and a C-terminal oligomerization domain, and they exhibit extensive sequence similarity at the catalytic domains. Due to the scarcity of the enzyme in animal tissues and its instability in vitro, TPH is the least characterized enzyme of the three aromatic amino acid hydroxylases. Although significant progress has been reported recently on the structural characterization of both TH (4) and PAH (5-7), the three-dimensional (3D) structure of TPH is still not known. The difficulties encountered in the crystallization of this enzyme seem to be related to its instability and insolubility, notably when it is expressed in bacterial systems (8). However, the catalytic domain of the enzyme from different sources, including the human brain, appears to be more stable, and several groups have reported its purification and characterization (9). Recently, stable full-length TPH forms from the human pineal gland (10) and the human parasite Schistosoma mansoni (11) have been cloned, expressed, and successfully isolated. The first observable product from the pterin cofactor in the TPH reaction is a 4a-hydroxytetrahydropterin, in which the oxygen atom a

Transcriptional networks in at-risk individuals identify signatures of type 1 diabetes progression.

Type 1 diabetes (T1D) is a disease of insulin deficiency that results from autoimmune destruction of pancreatic islet β cells. The exact cause of T1D remains unknown, although asymptomatic islet autoimmunity lasting from weeks to years before diagnosis raises the possibility of intervention before the onset of clinical disease. The number, type, and titer of islet autoantibodies are associated with long-term disease risk but do not cause disease, and robust early predictors of individual progression to T1D onset remain elusive. The Environmental Determinants of Diabetes in the Young (TEDDY) consortium is a prospective cohort study aiming to determine genetic and environmental interactions causing T1D. Here, we analyzed longitudinal blood transcriptomes of 2013 samples from 400 individuals in the TEDDY study before both T1D and islet autoimmunity. We identified and interpreted age-associated gene expression changes in healthy infancy and age-independent changes tracking with progression to both T1D and islet autoimmunity, beginning before other evidence of islet autoimmunity was present. We combined multivariate longitudinal data in a Bayesian joint model to predict individual risk of T1D onset and validated the association of a natural killer cell signature with progression and the model's predictive performance on an additional 356 samples from 56 individuals in the independent Type 1 Diabetes Prediction and Prevention study. Together, our results indicate that T1D is characterized by early and longitudinal changes in gene expression, informing the immunopathology of disease progression and facilitating prediction of its course.The TEDDY Study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. This work supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR001082). KGCS is a Lister Prize fellow and is supported by a Wellcome Trust Senior Investigator award (200871/Z/16/Z). EFM is a Wellcome-Beit prize fellow (10406/Z/14/A) supported by the Wellcome Trust and Beit Foundation (10406/Z/14/Z) and by the National Institutes for Health Research Biomedical Research Centre (Cambridge). LPX’s affiliation changed after completion of the manuscript and is now Département d'informatique et de recherche opérationnelle, Université de Montréal, Montréal, Canada and Mila, Quebec Institute for Learning Algorithms, Montréal, Canada