The dynamics of HCV-specific antibody responses in HIV/HCV patients on long-term antiretroviral therapy

Antibody responses have not been fully characterised in chronically HIV/HCV patients receiving antiretroviral therapy (ART). Seventeen HIV/HCV patients receiving ART were followed for a median (range) interval of 597 (186–766) weeks. Prior to ART, HIV/HCV patients had lower levels of antibodies reactive with HCV core and JFH-1, and lower genotype cross-reactive neutralising antibodies (nAb) titres, than HCV patients. Levels of JFH-1 reactive antibody increased on ART, irrespective of CD4+ T-cell counts or changes in serum ALT levels. The appearance of nAb coincided with control of HCV viral replication in five HIV/HCV patients. In other patients, HCV viral loads remained elevated despite nAb responses. Sustained virological responses following HCV therapy were associated with reduced antibody responses to JFH-1 and core but elevated responses to non-structural proteins. We conclude that nAb responses alone may fail to clear HCV, but contribute to control of viral replication in some HIV/HCV patients responding to ART

Inertial Weldment of Rhenium and Inconel 718

Inertia welding has been found to be a successful method for joining pure rhenium to Inconel 718, and with additional experimentation, this process may have great potential for rocket nozzle applications. Refractory metals are ideally suited to this application, where high temperatures and oxidizing environment survivability is required, but not all of the thruster must be made of these materials, only the areas that require them. A bolted joint between the two metals is not ideal, especially for small thrusters where the mess of a bolted join will come at a steep price. A welded joint would be preferred for flight thrusters

Initial Results from the CHOOZ Long Baseline Reactor Neutrino Oscillation Experiment

Initial results are presented from CHOOZ, a long-baseline reactor-neutrino vacuum-oscillation experiment. Electron antineutrinos were detected by a liquid scintillation calorimeter located at a distance of about 1 km. The detector was constructed in a tunnel protected from cosmic rays by a 300 MWE rock overburden. This massive shielding strongly reduced potentially troublesome backgrounds due to cosmic-ray muons, leading to a background rate of about one event per day, more than an order of magnitude smaller than the observed neutrino signal. From the statistical agreement between detected and expected neutrino event rates, we find (at 90% confidence level) no evidence for neutrino oscillations in the electron antineutrino disappearance mode for the parameter region given approximately by deltam**2 > 0.9 10**(-3) eV**2 for maximum mixing and (sin(2 theta)**2) > 0.18 for large deltam**2.Comment: 13 pages, Latex, submitted to Physics Letters

Search for neutrino oscillations on a long base-line at the CHOOZ nuclear power station

This final article about the CHOOZ experiment presents a complete description of the electron antineutrino source and detector, the calibration methods and stability checks, the event reconstruction procedures and the Monte Carlo simulation. The data analysis, systematic effects and the methods used to reach our conclusions are fully discussed. Some new remarks are presented on the deduction of the confidence limits and on the correct treatment of systematic errors.Comment: 41 pages, 59 figures, Latex file, accepted for publication by Eur.Phys.J.

Limits on Neutrino Oscillations from the CHOOZ Experiment

We present new results based on the entire CHOOZ data sample. We find (at 90% confidence level) no evidence for neutrino oscillations in the anti_nue disappearance mode, for the parameter region given by approximately Delta m**2 > 7 x 10**-4 eV^2 for maximum mixing, and sin**2(2 theta) = 0.10 for large Delta m**2. Lower sensitivity results, based only on the comparison of the positron spectra from the two different-distance nuclear reactors, are also presented; these are independent of the absolute normalization of the anti_nue flux, the cross section, the number of target protons and the detector efficiencies.Comment: 19 pages, 11 figures, Latex fil

Determination of neutrino incoming direction in the CHOOZ experiment and Supernova explosion location by scintillator detectors

The CHOOZ experiment measured the antineutrino flux at a distance of about 1 Km from two nuclear reactors in order to detect possible neutrino oscillations with squared mass differences as low as 10**-3 eV**2 for full mixing. We show that the data analysis of the electron antineutrino events, collected by our liquid scintillation detector, locates the antineutrino source within a cone of half-aperture of about 18 degrees at the 68% C.L.. We discuss the implications of this experimental result for tracking down a supernova explosion.Comment: Submitted to Physical Review

Switching Heavy Chain Constant Domains Denatures the Paratope 3D Architecture of Influenza Monoclonal Antibodies

Several human monoclonal Abs for treating Influenza have been evaluated in clinical trials with limited success despite demonstrating superiority in preclinical animal models including mice. To conduct efficacy studies in mice, human monoclonal Abs are genetically engineered to contain mouse heavy chain constant domain to facilitate the engagement of Fc-receptors on mouse immune effector cells. Although studies have consistently reported discrepancies in Ab effectiveness following genetic engineering, the structural and mechanistic basis for these inconsistencies remain uncharacterized. Here, we use homology modeling to predict variable region (VR) analogous monoclonal Abs possessing human IgG1, mouse IgG1, and mouse IgG2a heavy chain constant domains. We then examine predicted 3D structures for variations in the spatial location and orientation of corresponding paratope amino acid residues. By structurally aligning crystal structures of Fabs in complex with hemagglutinin (HA), we show that corresponding paratope amino acid residues for VR-analogous human IgG1, mouse IgG1, and mouse IgG2a monoclonal Abs interact differentially with HA suggesting that their epitopes might not be identical. To demonstrate that variations in the paratope 3D fine architecture have implications for Ab specificity and effectiveness, we genetically engineered VR-analogous human IgG1, human IgG4, mouse IgG1, and mouse IgG2a monoclonal Abs and explored their specificity and effectiveness in protecting MDCK cells from infection by pandemic H1N1 and H3N2 Influenza viruses. We found that VR-analogous monoclonal Abs placed on mouse heavy chain constant domains were more efficacious at protecting MDCK cells from Influenza virus infection relative to those on human heavy chain constant domains. Interestingly, mouse but not human heavy chain constant domains increased target breadth in some monoclonal Abs. These data suggest that heavy chain constant domain sequences play a role in shaping Ab repertoires that go beyond class or sub-class differences in immune effector recruitment. This represents a facet of Ab biology that can potentially be exploited to improve the scope and utilization of current therapeutic or prophylactic candidates for influenza