Connective tissue activation. xxxv. detection of connective tissue activating peptide–iii isoforms in synovium from osteoarthritis and rheumatoid arthritis patients: patterns of interaction with other synovial cytokines in cell culture

Objective. To determine whether extracts of unincubated osteoarthritis (OA) and rheumatoid arthritis (RA) synovial tissue contain connective tissue activating peptide–III (CTAP-III) isoforms and prostaglandin E 2 (PGE 2 ), and whether such extracts have growth-promoting activity, and to determine whether binary combinations of CTAP-III with other cytokines reported to be present in synovial tissue lead to synergistic, additive, or inhibitory effects on growth. Methods. Acid–ethanol extracts of human synovium were examined for growth-promoting activity by measuring formation of 14 C-glycosaminoglycan ( 14 CGAG) and 3 H-DNA in synovial cell cultures; PGE 2 was measured by enzyme immunoassay, and CTAP-III isoforms were identified by Western blotting of extracted proteins separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Growth-promoting activity of CTAP-III and other cytokines was tested in synovial cultures treated with the agonists singly and in binary combination, by measuring changes in synthesis of 14 C-GAG and 3 H-DNA. Results. Platelet-derived CTAP-III and a cleavage isoform with the electrophoretic mobility of CTAP-III–des 1–15/neutrophil-activating peptide–2 (NAP-2) and PGE 2 were found in biologically active extracts of synovial samples from patients with RA and OA. Five growth factors (recombinant epidermal growth factor [rEGF], recombinant interleukin-1Β [rIL-1Β], basic fibroblast growth factor [bFGF], PGE 1 , and PGE 2 ) in binary combination with CTAP-III showed synergism in stimulating GAG synthesis; two (recombinant platelet-derived growth factor type BB [rPDGF-BB] and recombinant transforming growth factor Β [rTGFΒ]) had an additive effect. In combination with CTAP-III, rEGF and rPDGF-BB had a synergistic effect in promoting DNA synthesis, rTGFΒ and rbFGF had an additive effect, and rIL-1Β, PGE 1 , and PGE 2 were antagonistic. Conclusions. The results suggest that, in addition to endogenous factors, CTAP-III and other plateletderived cytokines may play roles in regulating synovial cell metabolism in RA and OA, and that combinations of growth factors may be more significant than single agents in amplification or suppression of important cell functions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37793/1/1780350712_ftp.pd

Connective tissue activation

Four normal (NF) and 4 scleroderma skin fibro-blast (SF) strains were compared with respect to 1) basal 14 C-glucosamine and 35 SO 4 -labeled glycosaminoglycan (GAG) synthesis, 2) responsiveness to autacoid mediators, and 3) performance following maximal stimulation. Under basal conditions, SF synthesized and secreted 2–3 times more radioactive hyaluronic acid than the NF ( P < 0.001); molecular volume by gel chromatography was similar and suggested a high molecular weight product. SF were essentially as responsive to normal lymphoid and platelet factors as were NF. No consistent qualitative or quantitative differences in sulfated GAG synthesis were noted between the 2 groups of cells. Incubation of NF and SF with a false “core protein” such as p-nitrophenyl-Β-D-xyloside suggested that synthesis of the core protein was rate limiting; SF and NF were equally facile in SO 4 -GAG chain synthesis in the presence of a Β-xyloside. SF appear to retain in vitro a partially activated state for many generations, at least with respect to hyaluronic acid synthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37761/1/1780261109_ftp.pd

Testing Hydrodynamic Models of LMC X-4 with UV and X-ray Spectra

We compare the predictions of hydrodynamic models of the LMC X-4 X-ray binary system with observations of UV P Cygni lines with the GHRS and STIS spectrographs on the Hubble Space Telescope. The hydrodynamic model determines density and velocity fields of the stellar wind, wind-compressed disk, accretion stream, Keplerian accretion disk, and accretion disk wind. We use a Monte Carlo code to determine the UV P Cygni line profiles by simulating the radiative transfer of UV photons that originate on the star and are scattered in the wind. The qualitative orbital variation predicted is similar to that observed, although the model fails to reproduce the strong orbital asymmetry (the observed absorption is strongest for phi>0.5). The model predicts a mid-eclipse X-ray spectrum, due almost entirely to Compton scattering, with a factor 4 less flux than observed with ASCA. We discuss how the model may need to be altered to explain the spectral variability of the system.Comment: 11 figures, accepted by Ap

Connective tissue activation. xxxvi. the origin, variety, distribution, and biologic fate of connective tissue activating peptide–iii isoforms: characteristics in patients with rheumatic, renal, and arterial disease

Objective. To determine the origin, distribution, and biologic fate of platelet-derived connective tissue activating peptide–III (CTAP-III), to define the relative amounts of the antigen forms (CTAP-III, betathromboglobulin [Β-TG], neutrophil activating peptide–2 [NAP-2]) in plasma of normal persons and those with rheumatic or end-stage renal disease, and to define the isoforms of CTAP-III in platelets, plasma, transudates, and tissue deposits. Methods. CTAP-III in plasma was measured by enzyme-linked immunosorbent assay, and growth promoting activity of CTAP-III isoforms was tested in synovial and peritoneal cell cultures by measuring increased synthesis of 14 C-glycosaminoglycan ( 14 C-GAG) and 3 H-DNA. Isolated CTAP-III was characterized by Western blotting, microsequencing, and mass spectrometry. Results. CTAP-III was the primary isoform of this antigen family in normal platelets and platelet-rich plasma; Β-TG and NAP-2 accounted for 90%), and Β-TG was the most rare (0–1%). Deposition of CTAP-III in tissues, such as synovium, spleen, and kidney, is associated with partial processing to NAP-2–like isoforms and the potential to induce neutrophil and fibroblast activation in patients with rheumatic or end-stage renal disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37798/1/1780360816_ftp.pd

Time Dependent Monte Carlo Radiative Transfer Calculations For 3-Dimensional Supernova Spectra, Lightcurves, and Polarization

We discuss Monte-Carlo techniques for addressing the 3-dimensional time-dependent radiative transfer problem in rapidly expanding supernova atmospheres. The transfer code SEDONA has been developed to calculate the lightcurves, spectra, and polarization of aspherical supernova models. From the onset of free-expansion in the supernova ejecta, SEDONA solves the radiative transfer problem self-consistently, including a detailed treatment of gamma-ray transfer from radioactive decay and with a radiative equilibrium solution of the temperature structure. Line fluorescence processes can also be treated directly. No free parameters need be adjusted in the radiative transfer calculation, providing a direct link between multi-dimensional hydrodynamical explosion models and observations. We describe the computational techniques applied in SEDONA, and verify the code by comparison to existing calculations. We find that convergence of the Monte Carlo method is rapid and stable even for complicated multi-dimensional configurations. We also investigate the accuracy of a few commonly applied approximations in supernova transfer, namely the stationarity approximation and the two-level atom expansion opacity formalism.Comment: 16 pages, ApJ accepte

Three-Dimensional Simulations of Inflows Irradiated by a Precessing Accretion Disk in Active Galactic Nuclei: Formation of Outflows

We present three-dimensional (3-D) hydrodynamical simulations of gas flows in the vicinity of an active galactic nucleus (AGN) powered by a precessing accretion disk. We consider the effects of the radiation force from such a disk on its environment on a relatively large scale (up to ~10 pc. We implicitly include the precessing disk by forcing the disk radiation field to precess around a symmetry axis with a given period ($P$) and a tilt angle ($\Theta$). We study time evolution of the flows irradiated by the disk, and investigate basic dependencies of the flow morphology, mass flux, angular momentum on different combinations of $\Theta$ and $P$. We find the gas flow settles into a configuration with two components, (1) an equatorial inflow and (2) a bipolar inflow/outflow with the outflow leaving the system along the poles (the directions of disk normals). However, the flow does not always reach a steady state. We find that the maximum outflow velocity and the kinetic outflow power at the outer boundary can be reduced significantly with increasing $\Theta$. We also find that of the mass inflow rate across the inner boundary does not change significantly with increasing $\Theta$. (Abbreviated)Comment: Accepted for publication in ApJ. 15 pages, 7 figures. A version with full resolution figures can be downloaded from http://www.physics.unlv.edu/~rk/preprint/precess.pd

Models of X-ray Photoionization in LMC X-4: Slices of a Stellar Wind

We show that the orbital variation in the UV P Cygni lines of the X-ray binary LMC X-4 results when X-rays photoionize nearly the entire region outside of the X-ray shadow of the normal star. We fit models to HST GHRS observations of N V and C IV P Cygni line profiles. Analytic methods assuming a spherically symmetric wind show that the wind velocity law is well-fit by v~(1-1/r)^beta, where beta is likely 1.4-1.6 and definitely <2.5. Escape probability models can fit the observed P Cygni profiles, and provide measurements of the stellar wind parameters. The fits determine Lx/Mdot=2.6+/-0.1 x10^43 erg/s/Msun yr, where Lx is the X-ray luminosity and Mdot is the mass-loss rate of the star. Allowing an inhomogeneous wind improves the fits. IUE spectra show greater P Cygni absorption during the second half of the orbit than during the first. We discuss possible causes of this effect.Comment: 56 pages, 12 figures, to be published in the Astrophysical Journa

Analysis of the Flux and Polarization Spectra of the Type Ia Supernova SN 2001el: Exploring the Geometry of the High-velocity Ejecta

SN 2001el is the first normal Type Ia supernova to show a strong, intrinsic polarization signal. In addition, during the epochs prior to maximum light, the CaII IR triplet absorption is seen distinctly and separately at both normal photospheric velocities and at very high velocities. The high-velocity triplet absorption is highly polarized, with a different polarization angle than the rest of the spectrum. The unique observation allows us to construct a relatively detailed picture of the layered geometrical structure of the supernova ejecta: in our interpretation, the ejecta layers near the photosphere (v \approx 10,000 km/s) obey a near axial symmetry, while a detached, high-velocity structure (v \approx 18,000-25,000 km/s) with high CaII line opacity deviates from the photospheric axisymmetry. By partially obscuring the underlying photosphere, the high-velocity structure causes a more incomplete cancellation of the polarization of the photospheric light, and so gives rise to the polarization peak and rotated polarization angle of the high-velocity IR triplet feature. In an effort to constrain the ejecta geometry, we develop a technique for calculating 3-D synthetic polarization spectra and use it to generate polarization profiles for several parameterized configurations. In particular, we examine the case where the inner ejecta layers are ellipsoidal and the outer, high-velocity structure is one of four possibilities: a spherical shell, an ellipsoidal shell, a clumped shell, or a toroid. The synthetic spectra rule out the spherical shell model, disfavor a toroid, and find a best fit with the clumped shell. We show further that different geometries can be more clearly discriminated if observations are obtained from several different lines of sight.Comment: 14 pages (emulateapj5) plus 18 figures, accepted by The Astrophysical Journa

Conservative formulations of general relativistic kinetic theory

Experience with core-collapse supernova simulations shows that accurate accounting of total particle number and 4-momentum can be a challenge for computational radiative transfer. This accurate accounting would be facilitated by the use of particle number and 4-momentum transport equations that allow transparent conversion between volume and surface integrals in both configuration and momentum space. Such conservative formulations of general relativistic kinetic theory in multiple spatial dimensions are presented in this paper, and their relevance to core-collapse supernova simulations is described.Comment: 48 page

Instabilities in the Envelopes and Winds of Very Massive Stars

The high luminosity of Very Massive Stars (VMS) means that radiative forces play an important, dynamical role both in the structure and stability of their stellar envelope, and in driving strong stellar-wind mass loss. Focusing on the interplay of radiative flux and opacity, with emphasis on key distinctions between continuum vs. line opacity, this chapter reviews instabilities in the envelopes and winds of VMS. Specifically, we discuss how: 1) the iron opacity bump can induce an extensive inflation of the stellar envelope; 2) the density dependence of mean opacity leads to strange mode instabilities in the outer envelope; 3) desaturation of line-opacity by acceleration of near-surface layers initiates and sustains a line-driven stellar wind outflow; 4) an associated line-deshadowing instability leads to extensive small-scale structure in the outer regions of such line-driven winds; 5) a star with super-Eddington luminosity can develop extensive atmospheric structure from photon bubble instabilities, or from stagnation of flow that exceeds the "photon tiring" limit; 6) the associated porosity leads to a reduction in opacity that can regulate the extreme mass loss of such continuum-driven winds. Two overall themes are the potential links of such instabilities to Luminous Blue Variable (LBV) stars, and the potential role of radiation forces in establishing the upper mass limit of VMS.Comment: 44 pages, 13 figures. Chapter to appear in the book "Very Massive Stars in the Local Universe", Springer, J.S. Vink, e