A Molecular Sensor To Characterize Arenavirus Envelope Glycoprotein Cleavage by Subtilisin Kexin Isozyme 1/Site 1 Protease.

UNLABELLED: Arenaviruses are emerging viruses including several causative agents of severe hemorrhagic fevers in humans. The advent of next-generation sequencing technology has greatly accelerated the discovery of novel arenavirus species. However, for many of these viruses, only genetic information is available, and their zoonotic disease potential remains unknown. During the arenavirus life cycle, processing of the viral envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) is crucial for productive infection. The ability of newly emerging arenaviruses to hijack human SKI-1/S1P appears, therefore, to be a requirement for efficient zoonotic transmission and human disease potential. Here we implement a newly developed cell-based molecular sensor for SKI-1/S1P to characterize the processing of arenavirus GPC-derived target sequences by human SKI-1/S1P in a quantitative manner. We show that only nine amino acids flanking the putative cleavage site are necessary and sufficient to accurately recapitulate the efficiency and subcellular location of arenavirus GPC processing. In a proof of concept, our sensor correctly predicts efficient processing of the GPC of the newly emergent pathogenic Lujo virus by human SKI-1/S1P and defines the exact cleavage site. Lastly, we employed our sensor to show efficient GPC processing of a panel of pathogenic and nonpathogenic New World arenaviruses, suggesting that GPC cleavage represents no barrier for zoonotic transmission of these pathogens. Our SKI-1/S1P sensor thus represents a rapid and robust test system for assessment of the processing of putative cleavage sites derived from the GPCs of newly discovered arenavirus by the SKI-1/S1P of humans or any other species, based solely on sequence information. IMPORTANCE: Arenaviruses are important emerging human pathogens that can cause severe hemorrhagic fevers with high mortality in humans. A crucial step in productive arenavirus infection of human cells is the processing of the viral envelope glycoprotein by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P). In order to break the species barrier during zoonotic transmission and cause severe disease in humans, newly emerging arenaviruses must be able to hijack human SKI-1/S1P efficiently. Here we implement a newly developed cell-based molecular sensor for human SKI-1/S1P to characterize the processing of arenavirus glycoproteins in a quantitative manner. We further use our sensor to correctly predict efficient processing of the glycoprotein of the newly emergent pathogenic Lujo virus by human SKI-1/S1P. Our sensor thus represents a rapid and robust test system with which to assess whether the glycoprotein of any newly emerging arenavirus can be efficiently processed by human SKI-1/S1P, based solely on sequence information

The 198Au beta-half-life in the metal Au revisited

The half-life of the beta-decay of 198Au has been measured for room temperature and 12 K. The resulting values of T(RT) = 2.684 +- 0.004 d and T(12 K) = 2.687 +- 0.005 d agree well within statistical uncertainties. An evidence for a temperature dependence of the half-life was not observed.Comment: accepted for publication in Eur. Phys. J.

The extended empirical process test for non-Gaussianity in the CMB, with an application to non-Gaussian inflationary models

In (Hansen et al. 2002) we presented a new approach for measuring non-Gaussianity of the Cosmic Microwave Background (CMB) anisotropy pattern, based on the multivariate empirical distribution function of the spherical harmonics a_lm of a CMB map. The present paper builds upon the same ideas and proposes several improvements and extensions. More precisely, we exploit the additional information on the random phases of the a_lm to provide further tests based on the empirical distribution function. Also we take advantage of the effect of rotations in improving the power of our procedures. The suggested tests are implemented on physically motivated models of non-Gaussian fields; Monte-Carlo simulations suggest that this approach may be very promising in the analysis of non-Gaussianity generated by non-standard models of inflation. We address also some experimentally meaningful situations, such as the presence of instrumental noise and a galactic cut in the map.Comment: 15 pages, 6 figures, submitted to Phys. Rev.

Aspects of the electroweak phase transition in the Minimal Supersymmetric Standard Model

We study the finite-temperature effective potential of the Minimal Supersymmetric Standard Model in the full (mA, tan(beta)) parameter space. As for the features of the electroweak phase transition, we identify two possible sources of significant differences with respect to the Standard Model: a stop sector with little supersymmetry breaking makes the phase transition more strongly first-order, whereas a light CP-odd neutral boson weakens its first-order nature. After including the leading plasma effects, T=0 radiative corrections due to top and stop loops, and the most important experimental constraints, we find that the danger of washing out any baryon asymmetry created at the electroweak scale is in general no less than in the Standard Model.Comment: 13 pages, 3 figures appended at the end as uuencoded ps-files, preprint CERN-TH.7057/9

Density pertubation of unparticle dark matter in the flat Universe

The unparticle has been suggested as a candidate of dark matter. We investigated the growth rate of the density perturbation for the unparticle dark matter in the flat Universe. First, we consider the model in which unparticle is the sole dark matter and find that the growth factor can be approximated well by $f=(1+3\omega_u)\Omega^{\gamma}_u$, where $\omega_u$ is the equation of state of unparticle. Our results show that the presence of $\omega_u$ modifies the behavior of the growth factor $f$. For the second model where unparticle co-exists with cold dark matter, the growth factor has a new approximation $f=(1+3\omega_u)\Omega^{\gamma}_u+\alpha \Omega_m$ and $\alpha$ is a function of $\omega_u$. Thus the growth factor of unparticle is quite different from that of usual dark matter. These information can help us know more about unparticle and the early evolution of the Universe.Comment: 6pages, 4 figures, accepted for publication in Eur. Phys. J.

Testing for non-Gaussianity of the cosmic microwave background in harmonic space: an empirical process approach

We present a new, model-independent approach for measuring non-Gaussianity of the Cosmic Microwave Background (CMB) anisotropy pattern. Our approach is based on the empirical distribution function of the normalized spherical harmonic expansion coefficients a_lm of a nearly full-sky CMB map, like the ones expected from forthcoming satellite experiments. Using a set of Kolmogorov-Smirnov type tests, we check for Gaussianity and independency of the a_lm. We test the method on two non-Gaussian toy-models of the CMB, one generated in spherical harmonic space and one in pixel (real) space. We also provide some rigorous results, possibly of independent interest, on the exact distribution of the spherical harmonic coefficients normalized by an estimated angular power spectrum.Comment: 29 pages, 7 figures, submitted to Phys. Rev.

Planck intermediate results. VIII. Filaments between interacting clusters

About half of the baryons of the Universe are expected to be in the form of filaments of hot and low density intergalactic medium. Most of these baryons remain undetected even by the most advanced X-ray observatories which are limited in sensitivity to the diffuse low density medium. The Planck satellite has provided hundreds of detections of the hot gas in clusters of galaxies via the thermal Sunyaev-Zel'dovich (tSZ) effect and is an ideal instrument for studying extended low density media through the tSZ effect. In this paper we use the Planck data to search for signatures of a fraction of these missing baryons between pairs of galaxy clusters. Cluster pairs are good candidates for searching for the hotter and denser phase of the intergalactic medium (which is more easily observed through the SZ effect). Using an X-ray catalogue of clusters and the Planck data, we select physical pairs of clusters as candidates. Using the Planck data we construct a local map of the tSZ effect centered on each pair of galaxy clusters. ROSAT data is used to construct X-ray maps of these pairs. After having modelled and subtracted the tSZ effect and X-ray emission for each cluster in the pair we study the residuals on both the SZ and X-ray maps. For the merging cluster pair A399-A401 we observe a significant tSZ effect signal in the intercluster region beyond the virial radii of the clusters. A joint X-ray SZ analysis allows us to constrain the temperature and density of this intercluster medium. We obtain a temperature of kT = 7.1 +- 0.9, keV (consistent with previous estimates) and a baryon density of (3.7 +- 0.2)x10^-4, cm^-3. The Planck satellite mission has provided the first SZ detection of the hot and diffuse intercluster gas.Comment: Accepted by A&

Planck 2015 results. XXVII. The Second Planck Catalogue of Sunyaev-Zeldovich Sources

We present the all-sky Planck catalogue of Sunyaev-Zeldovich (SZ) sources detected from the 29 month full-mission data. The catalogue (PSZ2) is the largest SZ-selected sample of galaxy clusters yet produced and the deepest all-sky catalogue of galaxy clusters. It contains 1653 detections, of which 1203 are confirmed clusters with identified counterparts in external data-sets, and is the first SZ-selected cluster survey containing > $10^3$ confirmed clusters. We present a detailed analysis of the survey selection function in terms of its completeness and statistical reliability, placing a lower limit of 83% on the purity. Using simulations, we find that the Y5R500 estimates are robust to pressure-profile variation and beam systematics, but accurate conversion to Y500 requires. the use of prior information on the cluster extent. We describe the multi-wavelength search for counterparts in ancillary data, which makes use of radio, microwave, infra-red, optical and X-ray data-sets, and which places emphasis on the robustness of the counterpart match. We discuss the physical properties of the new sample and identify a population of low-redshift X-ray under- luminous clusters revealed by SZ selection. These objects appear in optical and SZ surveys with consistent properties for their mass, but are almost absent from ROSAT X-ray selected samples