Avoiding bias in reconstructing the largest observable scales from partial-sky data

Obscuration due to Galactic emission complicates the extraction of information from cosmological surveys, and requires some combination of the (typically imperfect) modeling and subtraction of foregrounds, or the removal of part of the sky. This particularly affects the extraction of information from the largest observable scales. Maximum-likelihood estimators for reconstructing the full-sky spherical harmonic coefficients from partial-sky maps have recently been shown to be susceptible to contamination from within the sky cut, arising due to the necessity to band-limit the data by smoothing prior to reconstruction. Using the WMAP 7-year data, we investigate modified implementations of such estimators which are robust to the leakage of contaminants from within masked regions. We provide a measure, based on the expected amplitude of residual foregrounds, for selecting the most appropriate estimator for the task at hand. We explain why the related quadratic maximum-likelihood estimator of the angular power spectrum does not suffer from smoothing-induced bias.Comment: 8 pages, 8 figures. v2: replaced with version accepted by PRD (minor amendments to text only

Oncogenic fusion protein BCR-FGFR1 requires the breakpoint cluster region-mediated oligomerization and chaperonin Hsp90 for activation.

Mutation and translocation of fibroblast growth factor receptors often lead to aberrant signaling and cancer. This work focuses on the t(8;22)(p11;q11) chromosomal translocation which creates the breakpoint cluster region (BCR) fibroblast growth factor receptor1 (FGFR1) (BCR-FGFR1) fusion protein. This fusion occurs in stem cell leukemia/lymphoma, which can progress to atypical chronic myeloid leukemia, acute myeloid leukemia, or B-cell lymphoma. This work focuses on the biochemical characterization of BCR-FGFR1 and identification of novel therapeutic targets. The tyrosine kinase activity of FGFR1 is required for biological activity as shown using transformation assays, interleukin-3 independent cell proliferation, and liquid chromatography/mass spectroscopy analyses. Furthermore, BCR contributes a coiled-coil oligomerization domain, also essential for oncogenic transformation by BCR-FGFR1. The importance of salt bridge formation within the coiled-coil domain is demonstrated, as disruption of three salt bridges abrogates cellular transforming ability. Lastly, BCR-FGFR1 acts as a client of the chaperonin heat shock protein 90 (Hsp90), suggesting that BCR-FGFR1 relies on Hsp90 complex to evade proteasomal degradation. Transformed cells expressing BCR-FGFR1 are sensitive to the Hsp90 inhibitor Ganetespib, and also respond to combined treatment with Ganetespib plus the FGFR inhibitor BGJ398. Collectively, these data suggest novel therapeutic approaches for future stem cell leukemia/lymphoma treatment: inhibition of BCR oligomerization by disruption of required salt bridges; and inhibition of the chaperonin Hsp90 complex

Inverted initial conditions: Exploring the growth of cosmic structure and voids

We introduce and explore "paired" cosmological simulations. A pair consists of an A and B simulation with initial conditions related by the inversion δAðx; tinitialÞ ¼ −δBðx; tinitialÞ (underdensities substituted for overdensities and vice versa). We argue that the technique is valuable for improving our understanding of cosmic structure formation. The A and B fields are by definition equally likely draws from ΛCDM initial conditions, and in the linear regime evolve identically up to the overall sign. As nonlinear evolution takes hold, a region that collapses to form a halo in simulation A will tend to expand to create a void in simulation B. Applications include (i) contrasting the growth of A-halos and B-voids to test excursion-set theories of structure formation, (ii) cross-correlating the density field of the A and B universes as a novel test for perturbation theory, and (iii) canceling error terms by averaging power spectra between the two boxes. Generalizations of the method to more elaborate field transformations are suggested

Genetically modified haloes: towards controlled experiments in ΛCDM galaxy formation

We propose a method to generate ‘genetically modified’ (GM) initial conditions for high-resolution simulations of galaxy formation in a cosmological context. Building on the Hoffman–Ribak algorithm, we start from a reference simulation with fully random initial conditions, then make controlled changes to specific properties of a single halo (such as its mass and merger history). The algorithm demonstrably makes minimal changes to other properties of the halo and its environment, allowing us to isolate the impact of a given modification. As a significant improvement over previous work, we are able to calculate the abundance of the resulting objects relative to the reference simulation. Our approach can be applied to a wide range of cosmic structures and epochs; here we study two problems as a proof of concept. First, we investigate the change in density profile and concentration as the collapse times of three individual haloes are varied at fixed final mass, showing good agreement with previous statistical studies using large simulation suites. Secondly, we modify the z = 0 mass of haloes to show that our theoretical abundance calculations correctly recover the halo mass function. The results demonstrate that the technique is robust, opening the way to controlled experiments in galaxy formation using hydrodynamic zoom simulations

Cosmological Constraints on Dissipative Models of Inflation

(Abridged) We study dissipative inflation in the regime where the dissipative term takes a specific form, \Gamma=\Gamma(\phi), analyzing two models in the weak and strong dissipative regimes with a SUSY breaking potential. After developing intuition about the predictions from these models through analytic approximations, we compute the predicted cosmological observables through full numerical evolution of the equations of motion, relating the mass scale and scale of dissipation to the characteristic amplitude and shape of the primordial power spectrum. We then use Markov Chain Monte Carlo techniques to constrain a subset of the models with cosmological data from the cosmic microwave background (WMAP three-year data) and large scale structure (SDSS Luminous Red Galaxy power spectrum). We find that the posterior distributions of the dissipative parameters are highly non-Gaussian and their allowed ranges agree well with the expectations obtained using analytic approximations. In the weak regime, only the mass scale is tightly constrained; conversely, in the strong regime, only the dissipative coefficient is tightly constrained. A lower limit is seen on the inflation scale: a sub-Planckian inflaton is disfavoured by the data. In both weak and strong regimes, we reconstruct the limits on the primordial power spectrum and show that these models prefer a {\it red} spectrum, with no significant running of the index. We calculate the reheat temperature and show that the gravitino problem can be overcome with large dissipation, which in turn leads to large levels of non-Gaussianity: if dissipative inflation is to evade the gravitino problem, the predicted level of non-Gaussianity might be seen by the Planck satellite.Comment: 14 pages, 9 figures, Accepted by JCAP without text changes, References adde

Strong Lensing Probabilities in a Cosmological Model with a Running Primordial Power Spectrum

The combination of the first-year Wilkinson Microwave Anisotropy Probe (WMAP) data with other finer scale cosmic microwave background (CMB) experiments (CBI and ACBAR) and two structure formation measurements (2dFGRS and Lyman $\alpha$ forest) suggest a $\Lambda$CDM cosmological model with a running spectral power index of primordial density fluctuations. Motivated by this new result on the index of primordial power spectrum, we present the first study on the predicted lensing probabilities of image separation in a spatially flat $\Lambda$CDM model with a running spectral index (RSI-$\Lambda$CDM model). It is shown that the RSI-$\Lambda$CDM model suppress the predicted lensing probabilities on small splitting angles of less than about 4$^{''}$ compared with that of standard power-law $\Lambda$CDM (PL-$\Lambda$CDM) model.Comment: 11 pages including 1 figures. Accepted for publication in Modern Physics Letters A (MPLA), minor revision

The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles

Copyright @ 2008 American Society for Microbiology.The production of virus-like particles (VLPs) constitutes a relevant and safe model to study molecular determinants of virion egress. The minimal requirement for the assembly of VLPs for the coronavirus responsible for severe acute respiratory syndrome in humans (SARS-CoV) is still controversial. Recent studies have shown that SARS-CoV VLP formation depends on either M and E proteins or M and N proteins. Here we show that both E and N proteins must be coexpressed with M protein for the efficient production and release of VLPs by transfected Vero E6 cells. This suggests that the mechanism of SARS-CoV assembly differs from that of other studied coronaviruses, which only require M and E proteins for VLP formation. When coexpressed, the native envelope trimeric S glycoprotein is incorporated onto VLPs. Interestingly, when a fluorescent protein tag is added to the C-terminal end of N or S protein, but not M protein, the chimeric viral proteins can be assembled within VLPs and allow visualization of VLP production and trafficking in living cells by state-of-the-art imaging technologies. Fluorescent VLPs will be used further to investigate the role of cellular machineries during SARS-CoV egress.The University of Hong Kong and the French Ministry of Health