Falco Peregrinus Pealei in Ohio : An Error

Author Institution: Section of Ecology and Systematics, Langmuir Laboratory, Cornell University, Ithaca, New York 14805A specimen of peregrine falcon Falco peregrinus from Ohio, originally erroneously assigned to the Pacific Coast population F. p. pealei, is an individual of the nearly expirant eastern forest-inhabiting F. p. ana turn

Fluctuation Spectrum from a Scalar-Tensor Bimetric Gravity Theory

Predictions of the CMB spectrum from a bimetric gravity theory (gr-qc/0101126) are presented. The initial inflationary period in BGT is driven by a vanishingly small speed of gravitational waves v_g in the very early universe. This initial inflationary period is insensitive to the choice of scalar field potential and initial values of the scalar field. After this initial period of inflation, v_g will increase rapidly and the effects of a potential will become important. We show that a quadratic potential introduced into BGT yields an approximately flat spectrum with inflation parameters: n_s=0.98, n_t=-0.027, alpha_s=-3.2e-4 and alpha_t=-5.0e-4, with r >= 0.014.Comment: 14 pages, uses amsmath, amssym

Evolution of Phase-Space Density in Dark Matter Halos

The evolution of the phase-space density profile in dark matter (DM) halos is investigated by means of constrained simulations, designed to control the merging history of a given DM halo. Halos evolve through a series of quiescent phases of a slow accretion intermitted by violent events of major mergers. In the quiescent phases the density of the halo closely follows the NFW profile and the phase-space density profile, Q(r), is given by the Taylor & Navarro power law, r^{-beta}, where beta ~ 1.9 and stays remarkably stable over the Hubble time. Expressing the phase-space density by the NFW parameters, Q(r)=Qs (r/Rs)^{-beta}, the evolution of Q is determined by Qs. We have found that the effective mass surface density within Rs, Sigma_s = rhos Rs, remains constant throughout the evolution of a given DM halo along the main branch of its merging tree. This invariance entails that Qs ~ Rs^{-5/2} and Q(r) ~ Sigma_s^{-1/2} Rs^{-5/2} (r/ Rs)^{-beta}. It follows that the phase-space density remains constant, in the sense of Qs=const., in the quiescent phases and it decreases as Rs^{-5/2} in the violent ones. The physical origin of the NFW density profile and the phase-space density power law is still unknown. Yet, the numerical experiments show that halos recover these relations after the violent phases. The major mergers drive Rs to increase and Qs to decrease discontinuously while keeping Qs Rs^{5/2} = const. The virial equilibrium in the quiescent phases implies that a DM halos evolves along a sequence of NFW profiles with constant energy per unit volume (i.e., pressure) within Rs.Comment: 7 pages, 5 figures, accepted by the Astrophysical Journal. Revised, 2 figures adde

Structure Formation Inside Triaxial Dark Matter Halos: Galactic Disks, Bulges and Bars

We investigate the formation and evolution of galactic disks immersed in assembling live DM halos. Disk/halo components have been evolved from the cosmological initial conditions and represent the collapse of an isolated density perturbation. The baryons include gas (which participates in star formation [SF]) and stars. The feedback from the stellar energy release onto the ISM has been implemented. We find that (1) The growing triaxial halo figure tumbling is insignificant and the angular momentum (J) is channeled into the internal circulation; (2) Density response of the disk is out of phase with the DM, thus diluting the inner halo flatness and washing out its prolateness; (3) The total J is neathly conserved, even in models accounting for feedback; (4) The specific J for the DM is nearly constant, while that for baryons is decreasing; (5) Early stage of disk formation resembles the cat's cradle -- a small amorphous disk fueled via radial string patterns; (6) The initially puffed up gas component in the disk thins when the SF rate drops below ~5 Mo/yr; (7) About 40%-60% of the baryons remain outside the SF region; (8) Rotation curves appear to be flat and account for the observed disk/halo contributions; (9) A range of bulge-dominated to bulgeless disks was obtained; Lower density threshold for SF leads to a smaller, thicker disk; Gravitational softening in the gas has a substantial effect on various aspects of galaxy evolution and mimics a number of intrinsic processes within the ISM; (10) The models are characterized by an extensive bar-forming activity; (11) Nuclear bars, dynamically coupled and decoupled form in response to the gas inflow along the primary bars.Comment: 18 pages, 16 figures, accepted by the Astrophysical Journal. Minor revisions. The high-resolution figures can be found at http://www.pa.uky.edu/~shlosman/research/galdyn/figs07a

Inhibition of Ral GTPases Using a Stapled Peptide Approach

Aberrant Ras signalling drives numerous cancers and drugs to inhibit this are urgently required. This compelling clinical need, combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly and the focus has moved to the main downstream Ras-signalling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets, which were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development and there have therefore been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This therefore provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024

Inhibition of Ral GTPases Using a Stapled Peptide Approach.

Aberrant Ras signaling drives numerous cancers, and drugs to inhibit this are urgently required. This compelling clinical need combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly, and the focus has moved to the main downstream Ras-signaling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets that were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development, and there have, therefore, been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical-stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This, therefore, provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024

Constrained Cosmological Simulations of Dark Matter Halos

The formation and structure of dark matter (DM) halos is studied by means of constrained realizations of Gaussian fields using N-body simulations. A series of experiments of the formation of a 10^{12} Msun halo is designed to study the dependence of the density profile on its merging history. We confirm that the halo growth consists of violent and quiescent phases, with the density well approximated by the Navarro-Frenk-White (NFW) profile during the latter phases. We find that (1) the NFW scale radius R_s stays constant during the quiescent phase and grows abruptly during the violent one. In contrast, the virial radius grows linearly during the quiescent and abruptly during the violent phases. (2) The central density stays unchanged during the quiescent phase while dropping abruptly during the violent phase. (3) The value of \rs reflects the violent merging history of the halo, and depends on the number of violent events and their fractional magnitudes, independent of the time and order of these events. It does not reflect the formation time of the halo. (4) The fractional change in R_s is a nonlinear function of the fractional absorbed kinetic energy within R_s in a violent event.Comment: 5 pages, 2 postscript figures, ApJ emulator, submitted to ApJ Letter

A Two-Phase Innate Host Response to Alphavirus Infection Identified by mRNP-Tagging In Vivo

A concept fundamental to viral pathogenesis is that infection induces specific changes within the host cell, within specific tissues, or within the entire animal. These changes are reflected in a cascade of altered transcription patterns evident during infection. However, elucidation of this cascade in vivo has been limited by a general inability to distinguish changes occurring in the minority of infected cells from those in surrounding uninfected cells. To circumvent this inherent limitation of traditional gene expression profiling methods, an innovative mRNP-tagging technique was implemented to isolate host mRNA specifically from infected cells in vitro as well as in vivo following Venezuelan equine encephalitis virus (VEE) infection. This technique facilitated a direct characterization of the host defense response specifically within the first cells infected with VEE, while simultaneous total RNA analysis assessed the collective response of both the infected and uninfected cells. The result was a unique, multifaceted profile of the early response to VEE infection in primary dendritic cells, as well as in the draining lymph node, the initially targeted tissue in the mouse model. A dynamic environment of complex interactions was revealed, and suggested a two-step innate response in which activation of a subset of host genes in infected cells subsequently leads to activation of the surrounding uninfected cells. Our findings suggest that the application of viral mRNP-tagging systems, as introduced here, will facilitate a much more detailed understanding of the highly coordinated host response to infectious agents