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

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

Solid deuterium surface degradation at ultracold neutron sources

Solid deuterium (sD_2) is used as an efficient converter to produce ultracold neutrons (UCN). It is known that the sD_2 must be sufficiently cold, of high purity and mostly in its ortho-state in order to guarantee long lifetimes of UCN in the solid from which they are extracted into vacuum. Also the UCN transparency of the bulk sD_2 material must be high because crystal inhomogeneities limit the mean free path for elastic scattering and reduce the extraction efficiency. Observations at the UCN sources at Paul Scherrer Institute and at Los Alamos National Laboratory consistently show a decrease of the UCN yield with time of operation after initial preparation or later treatment (`conditioning') of the sD_2. We show that, in addition to the quality of the bulk sD_2, the quality of its surface is essential. Our observations and simulations support the view that the surface is deteriorating due to a build-up of D_2 frost-layers under pulsed operation which leads to strong albedo reflections of UCN and subsequent loss. We report results of UCN yield measurements, temperature and pressure behavior of deuterium during source operation and conditioning, and UCN transport simulations. This, together with optical observations of sD_2 frost formation on initially transparent sD_2 in offline studies with pulsed heat input at the North Carolina State University UCN source results in a consistent description of the UCN yield decrease.Comment: 15 pages, 22 figures, accepted by EPJ-

Disentangling protostellar evolutionary stages in clustered environments using Spitzer-IRS spectra and comprehensive SED modeling

When studying the evolutionary stages of protostars that form in clusters, the role of any intracluster medium cannot be neglected. High foreground extinction can lead to situations where young stellar objects (YSOs) appear to be in earlier evolutionary stages than they actually are, particularly when using simple criteria like spectral indices. To address this issue, we have assembled detailed SED characterizations of a sample of 56 Spitzer-identified candidate YSOs in the clusters NGC 2264 and IC 348. For these, we use spectra obtained with the Infrared Spectrograph onboard the Spitzer Space Telescope and ancillary multi-wavelength photometry. The primary aim is twofold: 1) to discuss the role of spectral features, particularly those due to ices and silicates, in determining a YSO's evolutionary stage, and 2) to perform comprehensive modeling of spectral energy distributions (SEDs) enhanced by the IRS data. The SEDs consist of ancillary optical-to-submillimeter multi-wavelength data as well as an accurate description of the 9.7 micron silicate feature and of the mid-infrared continuum derived from line-free parts of the IRS spectra. We find that using this approach, we can distinguish genuine protostars in the cluster from T Tauri stars masquerading as protostars due to external foreground extinction. Our results underline the importance of photometric data in the far-infrared/submillimeter wavelength range, at sufficiently high angular resolution to more accurately classify cluster members. Such observations are becoming possible now with the advent of the Herschel Space Observatory.Comment: Accepted for publication in Ap

Genetic relatedness of infecting and reinfecting respiratory syncytial virus strains identified in a birth cohort from rural Kenya

Background: Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear. Methods: Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections were identified by immunofluorescence testing of nasal washing samples collected during acute respiratory illnesses, typed into group A and B, and sequenced in the attachment (G) protein. A positive sample separated from a previous positive by ≥14 days was defined as a reinfection a priori. Results: Phylogenetic analysis was undertaken for 325 (80%) of 409 identified infections, including 53 (64%) of 83 reinfections. Heterologous group reinfections were observed in 28 episodes, and homologous group reinfections were observed in 25 episodes; 10 involved homologous genotypes, 5 showed no amino acid changes, and 3 were separated by 21–24 days and were potentially persistent infections. The temporal distribution of genotypes among reinfections did not differ from that of single infections. Conclusions: The vast majority of infection and reinfection pairs differed by group, genotype, or G amino acid sequence (ie, comprised distinct viruses). The extent to which this is a consequence of immune memory of infection history or prevalent diversity remains unclear

Anomalous diffusion modifies solar neutrino fluxes

Density and temperature conditions in the solar core suggest that the microscopic diffusion of electrons and ions could be nonstandard: Diffusion and friction coefficients are energy dependent, collisions are not two-body processes and retain memory beyond the single scattering event. A direct consequence of nonstandard diffusion is that the equilibrium energy distribution of particles departs from the Maxwellian one (tails goes to zero more slowly or faster than exponentially) modifying the reaction rates. This effect is qualitatively different from temperature and/or composition modification: Small changes in the number of particles in the distribution tails can strongly modify the rates without affecting bulk properties, such as the sound speed or hydrostatic equilibrium, which depend on the mean values from the distribution. This mechanism can considerably increase the range of predictions for the neutrino fluxes allowed by the current experimental values (cross sections and solar properties) and can be used to reduce the discrepancy between these predictions and the solar neutrino experiments.Comment: 16 pages, ReVTeX, no figures. Text partially revised (24 april 1998

Highly Variable Extinction and Accretion in the Jet-driving Class I Type Young Star PTF 10nvg (V2492 Cyg, IRAS 20496+4354)

We report extensive new photometry and spectroscopy of the highly variable young stellar object PTF 10nvg including optical and near-infrared time series data as well as mid-infrared and millimeter data. Following the previously reported 2010 rise, during 2011 and 2012 the source underwent additional episodes of brightening and dimming events including prolonged faint states. The observed high-amplitude variations are largely consistent with extinction changes having a 220 day quasi-periodic signal. Spectral evolution includes not only changes in the spectral slope but correlated variation in the prominence of TiO/VO/CO bands and atomic line emission, as well as anticorrelated variation in forbidden line emission which, along with H_2, dominates optical and infrared spectra at faint epochs. Neutral and singly-ionized atomic species are likely formed in an accretion flow and/or impact while the origin of zero-velocity atomic LiI 6707 in emission is unknown. Forbidden lines, including several rare species, exhibit blueshifted emission profiles and likely arise from an outflow/jet. Several of these lines are also seen spatially offset from the continuum source position, presumably in a shocked region of an extended jet. CARMA maps resolve on larger scales a spatially extended outflow in mm-wavelength CO. We attribute the observed photometric and spectroscopic behavior in terms of occultation of the central star as well as the bright inner disk and the accretion/outflow zones that renders shocked gas in the inner part of the jet amenable to observation at the faint epochs. We discuss PTF 10nvg as a source exhibiting both accretion-driven (perhaps analogous to V1647 Ori) and extinction-driven (perhaps analogous to UX Ori or GM Cep) high-amplitude variability phenomena.Comment: accepted to AJ - in press (74 pages

Duration of Protection against Malaria and Anaemia Provided by Intermittent Preventive Treatment in Infants in Navrongo, Ghana

BACKGROUND: Intermittent preventive treatment for malaria in Infants (IPTi) has been shown to give effective and safe protection against malaria. It has been suggested that IPTi might have long-lasting beneficial effects but, in most settings, the protection provided by IPTi appears to be short-lived. Knowledge of the duration of protection given by IPTi would help interpret the results of existing trials and suggest optimal delivery schedules for IPTi. This study investigated how the protective efficacy of IPTi against malaria and anaemia changes over time. METHODS AND FINDINGS: A secondary analysis of data from a cluster-randomised, placebo-controlled trial of IPTi using sulfadoxine-pyrimethamine (SP) in Ghana was conducted. In this trial IPTi was given to 2485 infants at 3, 4, 9 and 12 months of age; children remained in follow-up until two years of age. Poisson regression with a random effect to adjust for the cluster-randomised design was used to determine protective efficacy of IPTi against clinical malaria and anaemia in defined time strata following administration of IPTi. Analysis of first-or-only clinical malaria episode following the individual IPTi doses showed that some protection against malaria lasted between 4 to 6 weeks. A similar pattern was seen when the incidence of all malaria episodes up to 2 years of age was analysed in relation to the most recent IPT, by pooling the incidence of malaria after the individual IPTi doses. Protective efficacy within four weeks of IPTi was 75.2% (95% CI: 66-82) against malaria, 78.9% (95% CI: 69-86) against high parasite density malaria, and 93.8% (95% CI: 73-99) against anaemia. Protection against these outcomes was short-lived, with evidence of any effect lasting for only 6, 6 and 4 weeks respectively. Protection in children who were parasitaemic when receiving IPTi appeared to be of shorter duration than in uninfected children. There was no evidence of any benefit of IPTi after the immediate period following the IPTi doses. CONCLUSIONS: Intermittent preventive treatment provides considerable protection against malaria and anaemia for short periods, even in an area of intense seasonal transmission. Due to the relatively short duration of protection provided by each dose of IPTi, this treatment will be of most benefit when delivered at the time of peak malaria incidence