Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1

During the course of many chronic viral infections, the antiviral T cell response becomes attenuated through a process that is regulated in part by the host. While elevated expression of the immunosuppressive cytokine IL-10 is involved in the suppression of viral-specific T cell responses, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we traced IL-10 production over the course of chronic lymphocytic choriomeningitis virus (LCMV) infection in an IL-10 reporter mouse line. Using this model, we demonstrated that virus-specific T cells with reduced inflammatory function, particularly Th1 cells, display elevated and sustained IL-10 expression during chronic LCMV infection. Furthermore, ablation of IL-10 from the T cell compartment partially restored T cell function and reduced viral loads in LCMV-infected animals. We found that viral persistence is needed for sustained IL-10 production by Th1 cells and that the transcription factor BLIMP-1 is required for IL-10 expression by Th1 cells. Restimulation of Th1 cells from LCMV-infected mice promoted BLIMP-1 and subsequent IL-10 expression, suggesting that constant antigen exposure likely induces the BLIMP-1/IL-10 pathway during chronic viral infection. Together, these data indicate that effector T cells self-limit their responsiveness during persistent viral infection via an IL-10-dependent negative feedback loop.This work was supported by an Australian NHMRC Overseas Biomedical Postdoctoral Fellowship (to I.A. Parish); a Yale School of Medicine Brown-Coxe Postdoctoral Fellowship (to I.A. Parish); the Alexander von Humboldt Foundation (SKA2010, to P.A. Lang); a CIHR grant (to P.S. Ohashi); and by the Howard Hughes Medical Institute and NIH grant RO1AI074699 (to S.M. Kaech). P.S. Ohashi holds a Canada Research Chair in Autoimmunity and Tumor immunity

Classical phase space and statistical mechanics of identical particles

Starting from the quantum theory of identical particles, we show how to define a classical mechanics that retains information about the quantum statistics. We consider two examples of relevance for the quantum Hall effect: identical particles in the lowest Landau level, and vortices in the Chern-Simons Ginzburg-Landau model. In both cases the resulting {\em classical} statistical mechanics is shown to be a nontrivial classical limit of Haldane's exclusion statistics.Comment: 40 pages, Late

Unitary Equivalence of the Metric and Holonomy Formulations of 2+1 Dimensional Quantum Gravity on the Torus

Recent work on canonical transformations in quantum mechanics is applied to transform between the Moncrief metric formulation and the Witten-Carlip holonomy formulation of 2+1-dimensional quantum gravity on the torus. A non-polynomial factor ordering of the classical canonical transformation between the metric and holonomy variables is constructed which preserves their classical modular transformation properties. An extension of the definition of a unitary transformation is briefly discussed and is used to find the inner product in the holonomy variables which makes the canonical transformation unitary. This defines the Hilbert space in the Witten-Carlip formulation which is unitarily equivalent to the natural Hilbert space in the Moncrief formulation. In addition, gravitational theta-states arising from ``large'' diffeomorphisms are found in the theory.Comment: 31 pages LaTeX [Important Revision: a section is added constructing the inner product/Hilbert space for the Witten-Carlip holonomy formulation; the proof of unitary equivalence of the metric and holonomy formulations is then completed. Other additions include discussion of relation of canonical and unitary transformations. Title/abstract change.

Analytic Representation of Finite Quantum Systems

A transform between functions in R and functions in Zd is used to define the analogue of number and coherent states in the context of finite d-dimensional quantum systems. The coherent states are used to define an analytic representation in terms of theta functions. All states are represented by entire functions with growth of order 2, which have exactly d zeros in each cell. The analytic function of a state is constructed from its zeros. Results about the completeness of finite sets of coherent states within a cell are derived

Topology, Decoherence, and Semiclassical Gravity

We address the issue of recovering the time-dependent Schr\"{o}dinger equation from quantum gravity in a natural way. To reach this aim it is necessary to understand the nonoccurrence of certain superpositions in quantum gravity. We explore various possible explanations and their relation. These are the delocalisation of interference terms through interaction with irrelevant degrees of freedom (decoherence), gravitational anomalies, and the possibility of $\theta$ states. The discussion is carried out in both the geometrodynamical and connection representation of canonical quantum gravity.Comment: 18 pages, ZU-TH 3/93, to appear in Phys. Rev.

Vortices on Higher Genus Surfaces

We consider the topological interactions of vortices on general surfaces. If the genus of the surface is greater than zero, the handles can carry magnetic flux. The classical state of the vortices and the handles can be described by a mapping from the fundamental group to the unbroken gauge group. The allowed configurations must satisfy a relation induced by the fundamental group. Upon quantization, the handles can carry ``Cheshire charge.'' The motion of the vortices can be described by the braid group of the surface. How the motion of the vortices affects the state is analyzed in detail.Comment: 28 pages with 10 figures; uses phyzzx and psfig; Caltech preprint CALT-68-187

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

Testing spatial noncommutativiy via the Aharonov-Bohm effect

The possibility of detecting noncommutative space relics is analyzed using the Aharonov-Bohm effect. We show that, if space is noncommutative, the holonomy receives non-trivial kinematical corrections that will produce a diffraction pattern even when the magnetic flux is quantized. The scattering problem is also formulated, and the differential cross section is calculated. Our results can be extrapolated to high energy physics and the bound $\theta \sim [ 10 {TeV}]^{-2}$ is found. If this bound holds, then noncommutative effects could be explored in scattering experiments measuring differential cross sections for small angles. The bound state Aharonov- Bohm effect is also discussed.Comment: 16 pp, Revtex 4, 2 fig, new references added. To appear in PR

Partial Volume Segmentation of Brain MRI Scans of any Resolution and Contrast

Partial voluming (PV) is arguably the last crucial unsolved problem in Bayesian segmentation of brain MRI with probabilistic atlases. PV occurs when voxels contain multiple tissue classes, giving rise to image intensities that may not be representative of any one of the underlying classes. PV is particularly problematic for segmentation when there is a large resolution gap between the atlas and the test scan, e.g., when segmenting clinical scans with thick slices, or when using a high-resolution atlas. In this work, we present PV-SynthSeg, a convolutional neural network (CNN) that tackles this problem by directly learning a mapping between (possibly multi-modal) low resolution (LR) scans and underlying high resolution (HR) segmentations. PV-SynthSeg simulates LR images from HR label maps with a generative model of PV, and can be trained to segment scans of any desired target contrast and resolution, even for previously unseen modalities where neither images nor segmentations are available at training. PV-SynthSeg does not require any preprocessing, and runs in seconds. We demonstrate the accuracy and flexibility of the method with extensive experiments on three datasets and 2,680 scans. The code is available at https://github.com/BBillot/SynthSeg.Comment: accepted for MICCAI 202