Antigen depot is not required for alum adjuvanticity

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody. We demonstrate that alum and/or CpG adjuvants induced similar uptake of antigen, and in all cases, GFP signal did not persist beyond 24 h in draining lymph node antigen-presenting cells. Antigen presentation was first detectable on B cells within 6–12 h of antigen administration, followed by conventional dendritic cells (DCs) at 12–24 h, then finally plasmacytoid DCs at 48 h or later. Again, alum and/or CpG adjuvants did not have an effect on the magnitude or sequence of this response; furthermore, they induced similar antigen-specific T-cell activation in vivo. Notably, removal of the injection site and associated alum depot, as early as 2 h after administration, had no appreciable effect on antigen-specific T- and B-cell responses. This study clearly rules out a role for depot formation in alum adjuvant activity

Images in cardiovascular medicine : multiphoton microscopy for three-dimensional imaging of lymphocyte recruitment into apolipoprotein-E-deficient mouse carotid artery

Two recent elegant studies have shown that in apolipoprotein-E– deficient mice, the lamina adventitia is a major site of arterial wall inflammation associated with lymphocyte infiltration into atherosclerotic arteries and with formation of adventitial lymphoid-like tissues.1,2 These results suggest that lymphocyte responses in the lamina adventitia may play a crucial role in atherosclerosis development.1,

A technique for chronic repuncture micropuncture of dog kidney

The precision of kidney micropuncture for exploring changes in glomerular and tubular function was strikingly enhanced by the introduction of the repuncture and re-collection technique [1], thus permitting the use of each tubule as its own control. This procedure has allowed detection of changes in function that were not appreciated previously. However, the technical design of re-collection micropuncture is such that it is mainly applicable to the study of rapid and usually massive changes in homeostasis; exploration of the renal response to chronic, more physiologic maneuvers has been limited to clearance and non-repuncture micropuncture studies.This paper describes a technique for chronic repuncture micropuncture that allows repeat proximal tubule sampling in dogs at an interval of up to 14 days

Late-Type Stars in M31. I.: A Photometric Study of AGB Stars and Metallicity Gradients.

We have imaged five 7\arcmin \x 7\arcmin\ fields in M31 spanning galactocentric radii from 4 to 32 kpc along the SW-major axis. The fields were observed through two broad-band (\V\ and \I) and two narrow-band (\CN\ and \TiO) filters. The broad-band data were used to construct \IvsVI\ color-magnitude diagrams (CMDs) and, in some of our fields, we found significant numbers of stars in the Cepheid instability strip. A distance modulus for the Cepheids in the middle field was found that agreed well with other values in the literature values. The width of the giant branch (GB) in the \IvsVI\ CMD of all 5 fields was investigated, and we show that in four of the fields a likely explanation for the GB width is a combination of {\it both} metallicity and mass variations. Using the broad-band data, the asymptotic giant branch (AGB) luminosity functions (LFs) were measured in the five fields, and we show that differences exist between these LFs. We speculate on how the different star forming histories in the fields may lead to the observed AGB LFs and GB widths. Using the narrow-band data along with the broad-band data we separated the AGB stars into carbon-rich (C) and oxygen-rich (M) types. The carbon stars LFs were used to obtain an estimate for the distance modulus of M31 which agrees with the value derived from Cepheids. The ratio of C- to M-stars (C/M) is believed to be an indicator of gaseous chemical abundance at the time of formation of these stars. We show that the C/M ratio increases smoothly with galactocentric distance, suggesting an inverse correlation with metallicity. This is the first demonstration of this effect within a single extragalactic system. We find that differences in the width of the GB and the AGB LFs do not significantly affect the C/M ratio. We consider the effect of the increasing C/M ratio on the ISM in M31, and cite evidence in favor of a model where the grain composition in M31 is a function of galactocentric distance.Comment: UUencoded compressed postscript, 3 Figs. available on request. (Contact [email protected]

WIMP astronomy and particle physics with liquid-noble and cryogenic direct-detection experiments

Once weakly-interacting massive particles (WIMPs) are unambiguously detected in direct-detection experiments, the challenge will be to determine what one may infer from the data. Here, I examine the prospects for reconstructing the local speed distribution of WIMPs in addition to WIMP particle-physics properties (mass, cross sections) from next-generation cryogenic and liquid-noble direct-detection experiments. I find that the common method of fixing the form of the velocity distribution when estimating constraints on WIMP mass and cross sections means losing out on the information on the speed distribution contained in the data and may lead to biases in the inferred values of the particle-physics parameters. I show that using a more general, empirical form of the speed distribution can lead to good constraints on the speed distribution. Moreover, one can use Bayesian model-selection criteria to determine if a theoretically-inspired functional form for the speed distribution (such as a Maxwell-Boltzmann distribution) fits better than an empirical model. The shape of the degeneracy between WIMP mass and cross sections and their offset from the true values of those parameters depends on the hypothesis for the speed distribution, which has significant implications for consistency checks between direct-detection and collider data. In addition, I find that the uncertainties on theoretical parameters depends sensitively on the upper end of the energy range used for WIMP searches. Better constraints on the WIMP particle-physics parameters and speed distribution are obtained if the WIMP search is extended to higher energy (~ 1 MeV).Comment: 25 pages, 27 figures, matches published versio

The Herbertsmithite Hamiltonian: μ\muSR measurements on single crystals

We present transverse field muon spin rotation/relaxation measurements on single crystals of the spin-1/2 kagome antiferromagnet Herbertsmithite. We find that the spins are more easily polarized when the field is perpendicular to the kagome plane. We demonstrate that the difference in magnetization between the different directions cannot be accounted for by Dzyaloshinksii-Moriya type interactions alone, and that anisotropic axial interaction is present.Comment: 8 pages, 3 figures, accepted to JPCM special issue on geometrically frustrated magnetis

Kinetics and mechanism of proton transport across membrane nanopores

We use computer simulations to study the kinetics and mechanism of proton passage through a narrow-pore carbon-nanotube membrane separating reservoirs of liquid water. Free energy and rate constant calculations show that protons move across the membrane diffusively in single-file chains of hydrogen-bonded water molecules. Proton passage through the membrane is opposed by a high barrier along the effective potential, reflecting the large electrostatic penalty for desolvation and reminiscent of charge exclusion in biological water channels. At neutral pH, we estimate a translocation rate of about 1 proton per hour and tube.Comment: 4 pages, 4 figure