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

Characterization of Prototype BTeV Silicon Pixel Sensors Before and After Irradiation

We report on measurements performed on silicon pixel sensor prototypes exposed to a 200 MeV proton beam at the Indiana University Cyclotron Facility. The sensors are of n+/n/p+ type with multi-guard ring structures on the p+-side and p-stop electrode isolation on the n+-side. Electrical characterization of the devices was performed before and after irradiation up to a proton fluence of 4E14 p/cm2. We tested pixel sensors fabricated from normal and oxygen-enriched silicon wafers and with two different p-stop isolation layouts: common p-stop and individual p-stop.Comment: 8 pages in postscript format. Presented at 2001 IEEE Nuclear Science Symposium 4-10 November 2001 San Diego, Californi

The use of platelet-rich plasma for treatment of tenodesmic lesions in horses: A systematic review and meta-analysis of clinical and experimental data

The use of platelet-rich plasma (PRP) to enhance tenodesmic lesion healing has been questioned over the years. The aim of this study was to evaluate current literature to establish the effectiveness of PRP for treating tenodesmic lesions through a systematic review, in accordance with the PRISMA guidelines, and a meta-analysis. Studies comparing PRP with placebo or other treatments for horses with tenodesmic injuries or evaluated PRP effect on tendon and ligament explants were included. Outcomes were clinical, ultrasound, histologic, molecular evaluation, and adverse effects. Two authors independently extracted data and assessed each study’s risk of bias. Treatment effects were evaluated using risk ratios for dichotomous data, together with 95% CI. Data were pooled using the random-effects model. The quality of the evidence for each outcome was assessed using GRADE criteria. Twenty-four trials met inclusion criteria for systematic review, while fifteen studies were included in the meta-analysis. Results showed no significant differences in the outcomes between PRP and control groups. Finally, there is no definitive evidence that PRP enhances tendons and ligaments healing. Therefore, there is a need for more controlled trials to draw a firmer conclusion about the efficacy of PRP as a treatment for tenodesmic lesions in the horse

Molecular and Biological Analysis on Ommastrephes caroli Findings in the Central Western Mediterranean Sea (Sardinian Waters) Including First Age Investigation Using Eye Lenses and Beaks

Molecular identifications based on two mitochondrial markers (cytochrome c oxidase subunit I -COI- and 16S ribosomal RNA gene -16S-) have been implemented to confirm the morphological identification of eight specimens collected in the Central western Mediterranean. Molecular data show they belonged to a recently resurrected species of the genus Ommastrephes, i.e., O. caroli, known to be distributed in the Atlantic Ocean and Mediterranean Sea. Despite this, molecular analyses of COI sequences evidenced the presence of potential genetic differentiation between Mediterranean and Atlantic samples, highlighting the need for further studies, with more individuals to investigate the connectivity between individuals living in the two areas. Furthermore, morphological, biometric and reproductive features here reported, could be useful in evaluating possible distinctive biological features between the Mediterranean and Atlantic individuals. Female mature size was larger than the male. The relationships obtained between the beak measurements and body sizes (DML; TW) were better described by a power model. Asynchronous oocytes development with relatively small oocytes (0.05–1.10 mm) and a protracted intermittent spawning with active feeding were observed. This study also reported for the specie O. caroli the first data on the potential fecundity estimated (840061 oocytes), the oviducal load (90000 ripe oocytes) as well as the number of seminal receptacles and the size and morphology of the spermatangia found in the buccal mass of all mated females. Even if on a low sample size, beaks and eye lenses were used for the first time in O. caroli for age estimation. The statistically significant relationship found between increments counted in eye lenses and beaks highlighted the reliability of the lenses to estimate age in O. caroli, even if further studies will be needed for its validation. Assuming a daily increment for both structures, a mean life span of about 12–13 months was estimated for both sexes, which is consistent with the sexual maturity condition observed in all the samples and the semelparity known for cephalopods coleoids

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

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 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

Water Chemisorption and Reconstruction of the MgO Surface

The observed reactivity of MgO with water is in apparent conflict with theoretical calculations which show that molecular dissociation does not occur on a perfect (001) surface. We have performed ab-initio total energy calculations which show that a chemisorption reaction involving a reconstruction to form a (111) hydroxyl surface is strongly preferred with Delta E = -90.2kJ/mol. We conclude that protonation stabilizes the otherwise unstable (111) surface and that this, not the bare (001), is the most stable surface of MgO under ambient conditions.Comment: RevTeX, 4 pages, 1 Encapsulated Postscript Figur