Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes – NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases

The Air Microwave Yield (AMY) experiment - A laboratory measurement of the microwave emission from extensive air showers

The AMY experiment aims to measure the microwave bremsstrahlung radiation (MBR) emitted by air-showers secondary electrons accelerating in collisions with neutral molecules of the atmosphere. The measurements are performed using a beam of 510 MeV electrons at the Beam Test Facility (BTF) of Frascati INFN National Laboratories. The goal of the AMY experiment is to measure in laboratory conditions the yield and the spectrum of the GHz emission in the frequency range between 1 and 20 GHz. The final purpose is to characterise the process to be used in a next generation detectors of ultra-high energy cosmic rays. A description of the experimental setup and the first results are presented.Comment: 3 pages -- EPS-HEP'13 European Physical Society Conference on High Energy Physics (July, 18-24, 2013) at Stockholm, Swede

Performance of prototype BTeV silicon pixel detectors in a high energy pion beam

The silicon pixel vertex detector is a key element of the BTeV spectrometer. Sensors bump-bonded to prototype front-end devices were tested in a high energy pion beam at Fermilab. The spatial resolution and occupancies as a function of the pion incident angle were measured for various sensor-readout combinations. The data are compared with predictions from our Monte Carlo simulation and very good agreement is found.Comment: 24 pages, 20 figure

Beam Test Results of the BTeV Silicon Pixel Detector

The results of the BTeV silicon pixel detector beam test carried out at Fermilab in 1999-2000 are reported. The pixel detector spatial resolution has been studied as a function of track inclination, sensor bias, and readout threshold.Comment: 8 pages of text, 8 figures, Proceedings paper of Pixel 2000: International Workshop on Semiconductor Pixel Detectors for Particles and X-Rays, Genova, June 5-8, 200

Beam Test of BTeV Pixel Detectors

The silicon pixel vertex detector is one of the key elements of the BTeV spectrometer. Detector prototypes were tested in a beam at Fermilab. We report here on the measured spatial resolution as a function of the incident angles for different sensor-readout electronics combinations. We compare the results with predictions from our Monte Carlo simulation.Comment: 7 pages, 5 figures, Invited talk given by J.C. Wang at "Vertex 2000, 9th International Workshop on Vertex Detectors", Michigan, Sept 10-15, 2000. To be published in NIM

Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory

On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within $\pm 500$ s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Highlights from the Pierre Auger Observatory

The Pierre Auger Observatory is the world's largest cosmic ray observatory. Our current exposure reaches nearly 40,000 km$^2$ str and provides us with an unprecedented quality data set. The performance and stability of the detectors and their enhancements are described. Data analyses have led to a number of major breakthroughs. Among these we discuss the energy spectrum and the searches for large-scale anisotropies. We present analyses of our X$_{max}$ data and show how it can be interpreted in terms of mass composition. We also describe some new analyses that extract mass sensitive parameters from the 100% duty cycle SD data. A coherent interpretation of all these recent results opens new directions. The consequences regarding the cosmic ray composition and the properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray Conference, Rio de Janeiro 201

Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory

We report a multi-resolution search for anisotropies in the arrival directions of cosmic rays detected at the Pierre Auger Observatory with local zenith angles up to $80^\circ$ and energies in excess of 4 EeV ($4 \times 10^{18}$ eV). This search is conducted by measuring the angular power spectrum and performing a needlet wavelet analysis in two independent energy ranges. Both analyses are complementary since the angular power spectrum achieves a better performance in identifying large-scale patterns while the needlet wavelet analysis, considering the parameters used in this work, presents a higher efficiency in detecting smaller-scale anisotropies, potentially providing directional information on any observed anisotropies. No deviation from isotropy is observed on any angular scale in the energy range between 4 and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no other deviation from isotropy is observed for moments beyond the dipole one. The corresponding $p$-values obtained after accounting for searches blindly performed at several angular scales, are $1.3 \times 10^{-5}$ in the case of the angular power spectrum, and $2.5 \times 10^{-3}$ in the case of the needlet analysis. While these results are consistent with previous reports making use of the same data set, they provide extensions of the previous works through the thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report Numbe

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference, Beijing, China, August 201