Kinetics of the neutralizing antibody response to respiratory syncytial virus infections in a birth cohort

The kinetics of respiratory syncytial virus (RSV) neutralizing antibodies following birth, primary and secondary infections are poorly defined. The aims of the study were to measure and compare neutralizing antibody responses at different time points in a birth cohort followed-up over three RSV epidemics. Rural Kenyan children, recruited at birth between 2002 and 2003, were monitored for RSV infection over three epidemic seasons. Cord and 3-monthly sera, and acute and convalescent sera following RSV infection, were assayed in 28 children by plaque reduction neutralization test (PRNT). Relative to the neutralizing antibody titers of pre-exposure control sera (1.8 log10 PRNT), antibody titers following primary infection were (i) no different in sera collected between 0 and 0.4 months post-infection (1.9 log10 PRNT, P = 0.146), (ii) higher in sera collected between 0.5 and 0.9 (2.8 log10 PRNT, P < 0.0001), 1.0–1.9 (2.5 log10 PRNT, P < 0.0001), and 2.0–2.9 (2.3 log10 PRNT, P < 0.001) months post-infection, and (iii) no different in sera collected at between 3.0 and 3.9 months post-infection (2.0 log10 PRNT, P = 0.052). The early serum neutralizing response to secondary infection (3.02 log10 PRNT) was significantly greater than the early primary response (1.9 log10 PRNT, P < 0.0001). Variation in population-level virus transmission corresponded with changes in the mean cohort-level neutralizing titers. It is concluded that following primary RSV infection the neutralizing antibody response declines to pre-infection levels rapidly (∼3 months) which may facilitate repeat infection. The kinetics of the aggregate levels of acquired antibody reflect seasonal RSV occurrence, age, and infection history

On the Utility and Disutility of JEBAR

The usefulness of the concept of JEBAR, the joint effect of baroclinicity and relief, in large-scale ocean dynamics is critically analyzed. The authors address two questions. Does the JEBAR term properly characterize the joint impact of stratification and bottom topography on the ocean circulation? Do estimates of the JEBAR term from observational data allow reliable diagnostic calculations? The authors give a negative answer to the first question. The JEBAR term need not give a true measure of the effect of bottom relief in a stratified ocean. A simple two-layer model provides examples. As to the second question, it is demonstrated that the large-scale pattern of the transport streamfunction is captured by the smoothed solution, especially with the Mellor et al. formulation of the JEBAR term. However, the calculated velocity field is very noisy and the relative errors are large

Forbush decreases and turbulence levels at CME fronts

We seek to estimate the average level of MHD turbulence near coronal mass ejection (CME) fronts as they propagate from the Sun to the Earth. We examine the cosmic ray data from the GRAPES-3 tracking muon telescope at Ooty, together with the data from other sources for three well observed Forbush decrease events. Each of these events are associated with frontside halo Coronal Mass Ejections (CMEs) and near-Earth magnetic clouds. In each case, we estimate the magnitude of the Forbush decrease using a simple model for the diffusion of high energy protons through the largely closed field lines enclosing the CME as it expands and propagates from the Sun to the Earth. We use estimates of the cross-field diffusion coefficient $D_{\perp}$ derived from published results of extensive Monte Carlo simulations of cosmic rays propagating through turbulent magnetic fields. Our method helps constrain the ratio of energy density in the turbulent magnetic fields to that in the mean magnetic fields near the CME fronts. This ratio is found to be $\sim$ 2% for the 11 April 2001 Forbush decrease event, $\sim$ 6% for the 20 November 2003 Forbush decrease event and $\sim$ 249% for the much more energetic event of 29 October 2003.Comment: Accepted for publication in Astronomy and Astrophysics. (Abstract abridged) Typos correcte

Changes in the expression of the type 2 diabetes-associated gene VPS13C in the β cell are associated with glucose intolerance in humans and mice

Single nucleotide polymorphisms (SNPs) close to the VPS13C, C2CD4A and C2CD4B genes on chromosome 15q are associated with impaired fasting glucose and increased risk of type 2 diabetes. eQTL analysis revealed an association between possession of risk (C) alleles at a previously implicated causal SNP, rs7163757, and lowered VPS13C and C2CD4A levels in islets from female (n = 40, P < 0.041) but not from male subjects. Explored using promoter-reporter assays in β-cells and other cell lines, the risk variant at rs7163757 lowered enhancer activity. Mice deleted for Vps13c selectively in the β-cell were generated by crossing animals bearing a floxed allele at exon 1 to mice expressing Cre recombinase under Ins1 promoter control (Ins1Cre). Whereas Vps13cfl/fl:Ins1Cre (βVps13cKO) mice displayed normal weight gain compared with control littermates, deletion of Vps13c had little effect on glucose tolerance. Pancreatic histology revealed no significant change in β-cell mass in KO mice vs. controls, and glucose-stimulated insulin secretion from isolated islets was not altered in vitro between control and βVps13cKO mice. However, a tendency was observed in female null mice for lower insulin levels and β-cell function (HOMA-B) in vivo. Furthermore, glucose-stimulated increases in intracellular free Ca2+ were significantly increased in islets from female KO mice, suggesting impaired Ca2+ sensitivity of the secretory machinery. The present data thus provide evidence for a limited role for changes in VPS13C expression in conferring altered disease risk at this locus, particularly in females, and suggest that C2CD4A may also be involved

Relativistic Proton Production During the 14 July 2000 Solar Event: The Case for Multiple Source Mechanisms

Protons accelerated to relativistic energies by transient solar and interplanetary phenomena caused a ground-level cosmic ray enhancement on 14 July 2000, Bastille Day. Near-Earth spacecraft measured the proton flux directly and ground-based observatories measured the secondary responses to higher energy protons. We have modelled the arrival of these relativistic protons at Earth using a technique which deduces the spectrum, arrival direction and anisotropy of the high-energy protons that produce increased responses in neutron monitors. To investigate the acceleration processes involved we have employed theoretical shock and stochastic acceleration spectral forms in our fits to spacecraft and neutron monitor data. During the rising phase of the event (10:45 UT and 10:50 UT) we find that the spectrum between 140 MeV and 4 GeV is best fitted by a shock acceleration spectrum. In contrast, the spectrum at the peak (10:55 UT and 11:00 UT) and in the declining phase (11:40 UT) is best fitted with a stochastic acceleration spectrum. We propose that at least two acceleration processes were responsible for the production of relativistic protons during the Bastille Day solar event: (1) protons were accelerated to relativistic energies by a shock, presumably a coronal mass ejection (CME). (2) protons were also accelerated to relativistic energies by stochastic processes initiated by magnetohydrodynamic (MHD) turbulence.Comment: 38 pages, 9 figures, accepted for publication in the Astrophysical Journal, January, 200

Role of Flares and Shocks in Determining Solar Energetic Particle Abundances

We examine solar energetic particle (SEP) event-averaged abundances of Fe relative to O and intensity versus time profiles at energies above 25 MeV/nucleon using the SIS instrument on ACE. These data are compared with solar wind conditions during each event and with estimates of the strength of the associated shock based on average travel times to 1 AU. We find that the majority of events with an Fe to O abundance ratio greater than two times the average 5–12 MeV/nuc value for large SEP events (0.134) occur in the western hemisphere. Furthermore, in most of these Fe-rich events the profiles peak within 12 hours of the associated flare, suggesting that some of the observed interplanetary particles are accelerated in these flares. The vast majority of events with Fe/O below 0.134 are influenced by interplanetary shock acceleration. We suggest that variations in elemental composition in SEP events mainly arise from the combination of flare particles and shock acceleration of these particles and/or the ambient medium

Expansion of magnetic clouds in the outer heliosphere

A large amount of magnetized plasma is frequently ejected from the Sun as coronal mass ejections (CMEs). Some of these ejections are detected in the solar wind as magnetic clouds (MCs) that have flux rope signatures. Magnetic clouds are structures that typically expand in the inner heliosphere. We derive the expansion properties of MCs in the outer heliosphere from one to five astronomical units to compare them with those in the inner heliosphere. We analyze MCs observed by the Ulysses spacecraft using insitu magnetic field and plasma measurements. The MC boundaries are defined in the MC frame after defining the MC axis with a minimum variance method applied only to the flux rope structure. As in the inner heliosphere, a large fraction of the velocity profile within MCs is close to a linear function of time. This is indicative of} a self-similar expansion and a MC size that locally follows a power-law of the solar distance with an exponent called zeta. We derive the value of zeta from the insitu velocity data. We analyze separately the non-perturbed MCs (cases showing a linear velocity profile almost for the full event), and perturbed MCs (cases showing a strongly distorted velocity profile). We find that non-perturbed MCs expand with a similar non-dimensional expansion rate (zeta=1.05+-0.34), i.e. slightly faster than at the solar distance and in the inner heliosphere (zeta=0.91+-0.23). The subset of perturbed MCs expands, as in the inner heliosphere, at a significantly lower rate and with a larger dispersion (zeta=0.28+-0.52) as expected from the temporal evolution found in numerical simulations. This local measure of the expansion also agrees with the distribution with distance of MC size,mean magnetic field, and plasma parameters. The MCs interacting with a strong field region, e.g. another MC, have the most variable expansion rate (ranging from compression to over-expansion)

The Roles of Flares and Shocks in determining SEP Abundances

We examine solar energetic particle (SEP) event-averaged abundances of Fe relative to O and intensity versus time profiles at energies above 25 MeV/nucleon using the SIS instrument on ACE. These data are compared with solar wind conditions during each event and with estimates of the strength of the associated shock based on average travel times to 1 AU. We find that the majority of events with an Fe to 0 abundance ratio greater than two times the average 5-12 MeV/nuc value for large SEP events (0.134) occur in the western hemisphere. Furthermore, in most of these Fe-rich events the profiles peak within 12 hours of the associated flare, suggesting that some of the observed interplanetary particles are accelerated in these flares. The vast majority of events with Fe/O below 0.134 are influenced by interplanetary shock acceleration. We suggest that variations in elemental composition in SEP events mainly arise from the combination of flare particles and shock acceleration of these particles and/or the ambient medium