Bryostatin-1 vs. TPPB: Dose-Dependent APP Processing and PKC-α, -δ, and -ε Isoform Activation in SH-SY5Y Neuronal Cells

Activation of the α-secretase processing pathway of amyloid precursor protein (APP) is recognized as an important mechanism which diverts APP processing from production of beta-amyloid (Aβ) to non toxic sAPPα, decreasing Alzheimer’s disease (AD) plaque formation and AD-associated cognitive deficits. Two potent classes of PKC modulators can activate the α-secretase pathway, the benzo/indolactams and bryostatin/bryologues. While both modulate PKC-dependent APP processing, no direct comparisons of their relative pharmacological potencies have been accomplished which could assist in the development of AD therapies. In this study, we measured the activation of α-secretase APP processing and PKC-α, -δ, and -ε induced by the benzolactam-APP modulator TPPB and bryostatin-1 in the neuroblastoma cell line SH-SY5Y which expresses APP and α- and β-secretase processing mechanisms. Bryostatin-1 produced a more rapid, potent, and sustained activation of α-secretase APP processing than TPPB and selectively activated PKC-δ and PKC-ε. Although TPPB also activated α-secretase, its potency was approximately 10- to 100-fold lower, possibly reflecting lower PKC-δ and -ε activation. Because bryostatin-1 is a highly potent PKC-δ and -ε activator which activates α-secretase APP processing, further characterization of bryostatin-1/bryologues may help refine their use as important tools for the clinical management of AD

Detection of the 13CO(J=6-5) Transition in the Starburst Galaxy NGC 253

We report the detection of 13CO(J=6-5) emission from the nucleus of the starburst galaxy NGC 253 with the redshift (z) and Early Universe Spectrometer (ZEUS), a new submillimeter grating spectrometer. This is the first extragalactic detection of the 13CO(J=6-5) transition, which traces warm, dense molecular gas. We employ a multi-line LVG analysis and find ~ 35% - 60% of the molecular ISM is both warm (T ~ 110 K) and dense (n(H2) ~ 10^4 cm^-3). We analyze the potential heat sources, and conclude that UV and X-ray photons are unlikely to be energetically important. Instead, the molecular gas is most likely heated by an elevated density of cosmic rays or by the decay of supersonic turbulence through shocks. If the cosmic rays and turbulence are created by stellar feedback within the starburst, then our analysis suggests the starburst may be self-limiting.Comment: 4 pages, 2 figures, accepted by ApJ Letter

Neon Abundances from a Spitzer/IRS Survey of Wolf-Rayet Stars

We report on neon abundances derived from {\it Spitzer} high resolution spectral data of eight Wolf-Rayet (WR) stars using the forbidden line of [\ion{Ne}{3}] 15.56 microns. Our targets include four WN stars of subtypes 4--7, and four WC stars of subtypes 4--7. We derive ion fraction abundances $\gamma$ of Ne^{2+} for the winds of each star. The ion fraction abundance is a product of the ionization fraction $Q_{\rm i}$ in stage i and the abundance by number ${\cal A}_E$ of element E relative to all nuclei. Values generally consistent with solar are obtained for the WN stars, and values in excess of solar are obtained for the WC stars.Comment: to appear in Astrophysical Journa

On the Initial Mass Function of Population III Stars

The collapse and fragmentation of filamentary primordial gas clouds are explored using 1D and 2D hydrodynamical simulations coupled with the nonequilibrium processes of H2 formation. The simulations show that depending upon the initial density,there are two occasions for the fragmentation of primordial filaments. If a filament has relatively low initial density, the radial contraction is slow due to less effective H2 cooling. This filament tends to fragment into dense clumps before the central density reaches $10^{8-9}$ cm$^{-3}$, where H2 cooling by three-body reactions is effective and the fragment mass is more massive than some tens $M_\odot$. In contrast, if a filament is initially dense, the more effective H2 cooling with the help of three-body reactions allows the filament to contract up to $n\sim 10^{12}$ cm$^{-3}$. After the density reaches $n\sim 10^{12}$ cm$^{-3}$, the filament becomes optically thick to H2 lines and the radial contraction subsequently almost stops. At this final hydrostatic stage, the fragment mass is lowered down to $\approx 1M_\odot$ because of the high density of the filament. The dependence of the fragment mass upon the initial density could be translated into the dependence on the local amplitude of random Gaussian density fields or the epoch of the collapse of a parent cloud. Hence, it is predicted that the initial mass function of Population III stars is likely to be bimodal with peaks of $\approx 10^2 M_\odot$ and $\approx 1M_\odot$, where the relative heights could be a function of the collapse epoch.Comment: Accepted by Ap

Dynamics of Line-Driven Winds from Disks in Cataclysmic Variables. I. Solution Topology and Wind Geometry

We analyze the dynamics of 2-D stationary, line-driven winds from accretion disks in cataclysmic variable stars. The driving force is that of line radiation pressure, in the formalism developed by Castor, Abbott & Klein for O stars. Our main assumption is that wind helical streamlines lie on straight cones. We find that the Euler equation for the disk wind has two eigenvalues, the mass loss rate and the flow tilt angle with the disk. Both are calculated self-consistently. The wind is characterized by two distinct regions, an outer wind launched beyond four white dwarf radii from the rotation axis, and an inner wind launched within this radius. The inner wind is very steep, up to 80 degrees with the disk plane, while the outer wind has a typical tilt of 60 degrees. In both cases the ray dispersion is small. We, therefore, confirm the bi-conical geometry of disk winds as suggested by observations and kinematical modeling. The wind collimation angle appears to be robust and depends only on the disk temperature stratification. The flow critical points lie high above the disk for the inner wind, but close to the disk photosphere for the outer wind. Comparison with existing kinematical and dynamical models is provided. Mass loss rates from the disk as well as wind velocity laws are discussed in a subsequent paper.Comment: 21 pages, 10 Postscript figures; available also from http://www.pa.uky.edu/~shlosman/publ.html. Astrophysical Journal, submitte

Formation of Primordial Stars in a LCDM Universe

We study the formation of the first generation of stars in the standard cold dark matter model, using a very high-resolution hydordynamic simulations. Our simulation achieves a dynamic range of 10^{10} in length scale. With accurate treatment of atomic and molecular physics, it allows us to study the chemo-thermal evolution of primordial gas clouds to densities up to n = 10^{16}/cc without assuming any a priori equation of state; a six orders of magnitudes improvement over previous three-dimensional calculations. All the relevant atomic and molecular cooling and heating processes, including cooling by collision-induced continuum emission, are implemented. For calculating optically thick H2 cooling at high densities, we use the Sobolev method. To examine possible gas fragmentation owing to thermal instability, we compute explicitly the growth rate of isobaric perturbations. We show that the cloud core does not fragment in either the low-density or high-density regimes. We also show that the core remains stable against gravitational deformation and fragmentation. We obtain an accurate gas mass accretion rate within a 10 Msun innermost region around the protostar. The protostar is accreting the surrounding hot gas at a rate of 0.001-0.01 Msun/yr. From these findings we conclude that primordial stars formed in early minihalos are massive. We carry out proto-stellar evolution calculations using the obtained accretion rate. The resulting mass of the first star is M_ZAMS = 60-100 Msun, with the exact mass dependent on the actual accretion rate.Comment: 27 pages, 13 embedded figures. Revised versio

Physical State of Molecular Gas in High Galactic Latitude Translucent Clouds

The rotational transitions of carbon monoxide (CO) are the primary means of investigating the density and velocity structure of the molecular interstellar medium. Here we study the lowest four rotational transitions of CO towards high-latitude translucent molecular clouds (HLCs). We report new observations of the J = (4-3), (2-1), and (1-0) transitions of CO towards eight high-latitude clouds. The new observations are combined with data from the literature to show that the emission from all observed CO transitions is linearly correlated. This implies that the excitation conditions which lead to emission in these transitions are uniform throughout the clouds. Observed 13CO/12CO (1-0) integrated intensity ratios are generally much greater than the expected abundance ratio of the two species, indicating that the regions which emit 12CO (1-0) radiation are optically thick. We develop a statistical method to compare the observed line ratios with models of CO excitation and radiative transfer. This enables us to determine the most likely portion of the physical parameter space which is compatible with the observations. The model enables us to rule out CO gas temperatures greater than 30K since the most likely high-temperature configurations are 1 pc-sized structures aligned along the line of sight. The most probable solution is a high density and low temperature (HDLT) solution. The CO cell size is approximately 0.01 pc (2000 AU). These cells are thus tiny fragments within the 100 times larger CO-emitting extent of a typical high-latitude cloud. We discuss the physical implications of HDLT cells, and we suggest ways to test for their existence.Comment: 19 pages, 13 figures, 2 tables, emulateapj To be published in The Astrophysical Journa

Wolf-Rayet and LBV Nebulae as the Result of Variable and Non-Spherical Stellar Winds

The physical basis for interpreting observations of nebular morphology around massive stars in terms of the evolution of the central stars is reviewed, and examples are discussed, including NGC 6888, OMC-1, and eta Carinae.Comment: To be published in the Proceedings of IAU Colloquium 169 on Variable and Non-Spherical Stellar Winds in Luminous Hot Stars, ed. B. Wolf (Springer-Verlag, Berlin, Heidelberg). 7 pages, including 5 figures. A full-resolution version of fig 4 is available in the version at http://www.mpia-hd.mpg.de/theory/preprints.html#maclo

Molecular line radiative transfer in protoplanetary disks: Monte Carlo simulations versus approximate methods

We analyze the line radiative transfer in protoplanetary disks using several approximate methods and a well-tested Accelerated Monte Carlo code. A low-mass flaring disk model with uniform as well as stratified molecular abundances is adopted. Radiative transfer in low and high rotational lines of CO, C18O, HCO+, DCO+, HCN, CS, and H2CO is simulated. The corresponding excitation temperatures, synthetic spectra, and channel maps are derived and compared to the results of the Monte Carlo calculations. A simple scheme that describes the conditions of the line excitation for a chosen molecular transition is elaborated. We find that the simple LTE approach can safely be applied for the low molecular transitions only, while it significantly overestimates the intensities of the upper lines. In contrast, the Full Escape Probability (FEP) approximation can safely be used for the upper transitions (J_{\rm up} \ga 3) but it is not appropriate for the lowest transitions because of the maser effect. In general, the molecular lines in protoplanetary disks are partly subthermally excited and require more sophisticated approximate line radiative transfer methods. We analyze a number of approximate methods, namely, LVG, VEP (Vertical Escape Probability) and VOR (Vertical One Ray) and discuss their algorithms in detail. In addition, two modifications to the canonical Monte Carlo algorithm that allow a significant speed up of the line radiative transfer modeling in rotating configurations by a factor of 10--50 are described.Comment: 47 pages, 12 figures, accepted for publication in Ap

A Region of Violent Star Formation in the Irr Galaxy IC 10: Structure and Kinematics of Ionized and Neutral Gas

We have used observations of the galaxy IC 10 at the 6-m telescope of the Special Astrophysical Observatory with the SCORPIO focal reducer in the Fabry-Perot interferometer mode and with the MPFS spectrograph to study the structure and kinematics of ionized gas in the central region of current intense star formation. Archive VLA 21-cm observations are used to analyze the structure and kinematics of neutral gas in this region. High-velocity wings of the H-alpha and [SII] emission lines were revealed in the inner cavity of the nebula HL 111 and in other parts of the complex of violent star formation. We have discovered local expanding neutral-gas shells around the nebulae HL 111 and HL 106.Comment: 22 pages, 10 figures; accepted in Astronomy Report