Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques

Background: Live attenuated simian immunodeficiency virus (SIV) vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation. Methodology/Principal Findings: Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC) and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I /II haplotype or TRIM5α polymorphism and study outcome was identified. Conclusion/Significance: This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s) of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system

Collisional and thermal ionization of sodium Rydberg atoms I. Experiment for nS and nD atoms with n=8-20

Collisional and thermal ionization of sodium nS and nD Rydberg atoms with n=8-20 has been studied. The experiments were performed using a two-step pulsed laser excitation in an effusive atomic beam at atom density of about 2 10^{10} cm^{-3}. Molecular and atomic ions from associative, Penning, and thermal ionization processes were detected. It has been found that the atomic ions were created mainly due to photoionization of Rydberg atoms by photons of blackbody radiation at the ambient temperature of 300K. Blackbody ionization rates and effective lifetimes of Rydberg states of interest were determined. The molecular ions were found to be from associative ionization in Na(nL)+Na(3S) collisions. Rate constants of associative ionization have been measured using an original method based on relative measurements of Na_{2}^{+} and Na^{+} ion signals.Comment: 23 pages, 10 figure

Atomic excitation during recollision-free ultrafast multi-electron tunnel ionization

Modern intense ultrafast pulsed lasers generate an electric field of sufficient strength to permit tunnel ionization of the valence electrons in atoms. This process is usually treated as a rapid succession of isolated events, in which the states of the remaining electrons are neglected. Such electronic interactions are predicted to be weak, the exception being recollision excitation and ionization caused by linearly-polarized radiation. In contrast, it has recently been suggested that intense field ionization may be accompanied by a two-stage `shake-up' reaction. Here we report a unique combination of experimental techniques that enables us to accurately measure the tunnel ionization probability for argon exposed to 50 femtosecond laser pulses. Most significantly for the current study, this measurement is independent of the optical focal geometry, equivalent to a homogenous electric field. Furthermore, circularly-polarized radiation negates recollision. The present measurements indicate that tunnel ionization results in simultaneous excitation of one or more remaining electrons through shake-up. From an atomic physics standpoint, it may be possible to induce ionization from specific states, and will influence the development of coherent attosecond XUV radiation sources. Such pulses have vital scientific and economic potential in areas such as high-resolution imaging of in-vivo cells and nanoscale XUV lithography.Comment: 17 pages, 4 figures, original format as accepted by Nature Physic

Who Watches the Watchmen? An Appraisal of Benchmarks for Multiple Sequence Alignment

Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult to assess in those analyses. To compare the performance of different aligners and help detect systematic errors in alignments, a number of benchmarking strategies have been pursued. Here we present an overview of the main strategies--based on simulation, consistency, protein structure, and phylogeny--and discuss their different advantages and associated risks. We outline a set of desirable characteristics for effective benchmarking, and evaluate each strategy in light of them. We conclude that there is currently no universally applicable means of benchmarking MSA, and that developers and users of alignment tools should base their choice of benchmark depending on the context of application--with a keen awareness of the assumptions underlying each benchmarking strategy.Comment: Revie

Method for evaluating the snagging propensity of roofing membranes in buildings by roosting bats

Many buildings suitable as bat roosts contain synthetic roofing materials, hereafter referred to as Non-Bitumen Coated Roofing Membranes (NBCRMs) - this includes Breathable Roofing Membranes (BRMs) and non-Permeable Roofing Membranes (nPRMs), rather than 1F felts. Building regulations require all construction materials to be fit for purpose, but some BRMs (although appropriate for their intended purpose) can potentially threaten the viability of existing, legally protected roosts because of the way bats physically interact with their surface. With the assistance of the Isle of Wight Bat Hospital and real-world observations of how bats physically interact with NBCRMs within a roof void, we present a new laboratory test method capable of reproducing the progressive disintegration of NBCRM surfaces due to the plucking effect of bat claws. The resistance to NBCRM disintegration was characterised using a modified laboratory fabric pilling box test method. The method reproduced the ‘fluffing’ effects and projections of loops of filaments on the surface of BRMs that have been observed within bat roosts. It was established that spunbond nonwoven BRMs, can be highly susceptible to surface disintegration. The newly developed method is intended to aid selection of NBCRMs that reduce the risk to bats in their roosts, promoting bat conservation

Modeling the Seasonal Variability of the Plasma Environment in Saturn's Magnetosphere between Main Rings and Mimas

The detection of O2+ and O+ ions over Saturn's main rings by the Cassini INMS and CAPS instruments at Saturn orbit insertion (SOI) in 2004 confirmed the existence of the ring atmosphere and ionosphere. The source mechanism was suggested to be primarily photolytic decomposition of water ice producing neutral O2 and H2 (Johnson et al., 2006). Therefore, we predicted that there would be seasonal variations in the ring atmosphere and ionosphere due to the orientation of the ring plane to the sun (Tseng et al., 2010). The atoms and molecules scattered out of the ring atmosphere by ion-molecule collisions are an important source for the inner magnetosphere (Johnson et al., 2006; Martens et al. 2008; Tseng et al., 2010 and 2011). This source competes with water products from the Enceladus' plumes, which, although possibly variable, do not appear to have a seasonal variability (Smith et al., 2010). Recently, we found that the plasma density, composition and temperature in the region from 2.5 to 3.5 RS exhibited significant seasonal variation between 2004 and 2010 (Elrod et al., 2011). Here we present a one-box ion chemistry model to explain the complex and highly variable plasma environment observed by the CAPS instrument on Cassini. We combine the water products from Enceladus with the molecules scattered from a corrected ring atmosphere, in order to describe the temporal changes in ion densities, composition and temperature detected by CAPS. We found that the observed temporal variations are primarily seasonal, due to the predicted seasonal variation in the ring atmosphere, and are consistent with a compressed magnetosphere at SOI.Comment: This is submitted to P&S