Dedication of the Palomar Observatory and the Hale Telescope

The dedication of the Palomar Observatory, if it were being held in England, would be accompanied by brilliant pageantry both of the state, with its knights, heralds, pursuivants, kings at arms, admirals and captains, and of the church with its bishops, priests and deacons, crucifiers and choirs; and I am sure that we feel the quality of religion in this ceremony. We would hear the choirs chanting in antiphony that great canticle which so delights the choir boys: Benedicite, omnia opera Domini

AEC Research and Development Report

Introduction: The objective of Project Agreement 22 is to determine the feasibility of covering the complete reactor neutron flux start range from 10(3) - 5 x 10(13) nv by using in-core chambers. The counting mode of operating will be used at low neutron fluxes and the root mean square voltage fluctuation mode will be used at high neutron flux levels. Experiments have been run utilizing various ion chambers, gases, gas pressures, voltage, and cables to measure sensitivities and range operating in the counting and RMS voltage modes. Theoretical discussions are presented showing how the RMS voltage is related to individual pulse at both amplifier input and output. Noise is also compared at amplifier output so that the optimum bandwidth can be selected. Spectral shifts with changes in applied voltage causing signal variations have been examined and can be eliminated by appropriate selection of amplifier bandwidth. In the counting mode, all experiments have been conducted with unterminated cable. The chamber has been designed with geometry, gas, and pressure to completely stop fission fragments in the gas and hence maximize the charge generated in the chamber. Cables have been selected to minimize capacity. Various gases, pressures, and voltages have been used to determine that an optimum design has been achieved

MEAN SQUARE VOLTAGE FLUCTUATION MEASUREMENTS WITH NEUTRON-SENSITIVE ION CHAMBERS

The mean square fluctuation voltage in neutron sensitiv ion chambers was measured rather than the d-c current to improve gamma discrimination and eliminate d-c cable leakage interference currents. The circuitry and chambe are described, and performance in the mean square volta mode is compared with that in the d-c current mode. (D.C.W.

Electron emission into dielectric liquids

The current between polished nickel electrodes immersed in pure toluene has been measured as a function of electric field (over the range 0 to 250,000 volts/cm) and of temperature (from - 15 to 70°C). The Richardson lines are straight but show a very small slope (0.05 to 0.4 ev) and a small value of the constant A (10^-9 to 10^-11 amp./cm^2 deg.^2). The logi vs. E1 / 2 curves show a slope about twice the value e3 / 2 / D1 / 2kT predicted by the simple Schottky theory, but in agreement with the theory of Baker and Boltz. It is found however that there are serious objections to this theory, and the agreement with it is probably accidental. The situation is in fact too complex to be handled by a simple theory. It is suggested that for the low potential barrier present at the metal-dielectric interface a combination of thermionic and field currents would be expected which would account qualitatively for the observed behavior

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison

Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag–pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40 % of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100 % concordance with FAVN and strongly correlated with neutralization titres (r2=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or β-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 μl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies

Bile Acids Specifically Increase Hepatitis C Virus RNA-Replication

<div><h3>Background</h3><p>Hepatitis C virus (HCV) patients with high serum levels of bile acids (BAs) respond poorly to IFN therapy. BAs have been shown to increase RNA-replication of genotype 1 but not genotype 2a replicons. Since BAs modulate lipid metabolism including lipoprotein secretion and as HCV depends on lipids and lipoproteins during RNA-replication, virus production and cell entry, BAs may affect multiple steps of the HCV life cycle. Therefore, we analyzed the influence of BAs on individual steps of virus replication.</p> <h3>Methods</h3><p>We measured replication of subgenomic genotype (GT) 1b and 2a RNAs as well as full-length GT2a genomes in the presence of BAs using quantitative RT-PCR and luciferase assays. Cell entry was determined using HCV pseudoparticles (HCVpp). Virus assembly and release were quantified using a core-specific ELISA. Replicon chimeras were employed to characterize genotype-specific modulation of HCV by BAs. Lunet CD81/GFP-NLS-MAVS cells were used to determine infection of Con1 particles.</p> <h3>Results</h3><p>BAs increased RNA-replication of GT1b replicons up to 10-fold but had no effect on subgenomic GT2a replicons both in Huh-7 and HuH6 cells. They did not increase viral RNA translation, virus assembly and release or cell entry. Lowering replication efficiency of GT2a replicons rendered them susceptible to stimulation by BAs. Moreover, replication of full length GT1b with or without replication enhancing mutations and GT2a genomes were also stimulated by BAs.</p> <h3>Conclusions</h3><p>Bile acids specifically enhance RNA-replication. This is not limited to GT1, but also holds true for GT2a full length genomes and subgenomic replicons with low replication capacity. The increase of HCV replication by BAs may influence the efficacy of antiviral treatment in vivo and may improve replication of primary HCV genomes in cell culture.</p> </div