Role of LAG-3 in Regulatory T Cells

AbstractRegulatory T cells (Tregs) limit autoimmunity but also attenuate the magnitude of antipathogen and antitumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Tregs in vivo requires identification of Treg-selective receptors. A comparative analysis of gene expression arrays from antigen-specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg-selective expression of LAG-3, a CD4-related molecule that binds MHC class II. Antibodies to LAG-3 inhibit suppression by induced Tregs both in vitro and in vivo. Natural CD4+CD25+ Tregs express LAG-3 upon activation, which is significantly enhanced in the presence of effector cells, whereas CD4+CD25+ Tregs from LAG-3−/− mice exhibit reduced regulatory activity. Lastly, ectopic expression of LAG-3 on CD4+ T cells significantly reduces their proliferative capacity and confers on them suppressor activity toward effector T cells. We propose that LAG-3 marks regulatory T cell populations and contributes to their suppressor activity

Universal features of the order-parameter fluctuations : reversible and irreversible aggregation

We discuss the universal scaling laws of order parameter fluctuations in any system in which the second-order critical behaviour can be identified. These scaling laws can be derived rigorously for equilibrium systems when combined with the finite-size scaling analysis. The relation between order parameter, criticality and scaling law of fluctuations has been established and the connexion between the scaling function and the critical exponents has been found. We give examples in out-of-equilibrium aggregation models such as the Smoluchowski kinetic equations, or of at-equilibrium Ising and percolation models.Comment: 19 pages, 10 figure

Data challenges of time domain astronomy

Astronomy has been at the forefront of the development of the techniques and methodologies of data intensive science for over a decade with large sky surveys and distributed efforts such as the Virtual Observatory. However, it faces a new data deluge with the next generation of synoptic sky surveys which are opening up the time domain for discovery and exploration. This brings both new scientific opportunities and fresh challenges, in terms of data rates from robotic telescopes and exponential complexity in linked data, but also for data mining algorithms used in classification and decision making. In this paper, we describe how an informatics-based approach-part of the so-called "fourth paradigm" of scientific discovery-is emerging to deal with these. We review our experiences with the Palomar-Quest and Catalina Real-Time Transient Sky Surveys; in particular, addressing the issue of the heterogeneity of data associated with transient astronomical events (and other sensor networks) and how to manage and analyze it.Comment: 15 pages, 3 figures, to appear in special issue of Distributed and Parallel Databases on Data Intensive eScienc

Recent Advances in Understanding Particle Acceleration Processes in Solar Flares

We review basic theoretical concepts in particle acceleration, with particular emphasis on processes likely to occur in regions of magnetic reconnection. Several new developments are discussed, including detailed studies of reconnection in three-dimensional magnetic field configurations (e.g., current sheets, collapsing traps, separatrix regions) and stochastic acceleration in a turbulent environment. Fluid, test-particle, and particle-in-cell approaches are used and results compared. While these studies show considerable promise in accounting for the various observational manifestations of solar flares, they are limited by a number of factors, mostly relating to available computational power. Not the least of these issues is the need to explicitly incorporate the electrodynamic feedback of the accelerated particles themselves on the environment in which they are accelerated. A brief prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

QED Effects in Heavy Few-Electron Ions

Accurate calculations of the binding energies, the hyperfine splitting, the bound-electron g-factor, and the parity nonconservation effects in heavy few-electron ions are considered. The calculations include the relativistic, quantum electrodynamic (QED), electron-correlation, and nuclear effects. The theoretical results are compared with available experimental data. A special attention is focused on tests of QED in a strong Coulomb field.Comment: 28 pages, 6 tables, 5 figure

Particle Acceleration in Pulsar Wind Nebulae: PIC modelling

We discuss the role of particle-in-cell (PIC) simulations in unveiling the origin of the emitting particles in PWNe. After describing the basics of the PIC technique, we summarize its implications for the quiescent and the flaring emission of the Crab Nebula, as a prototype of PWNe. A consensus seems to be emerging that, in addition to the standard scenario of particle acceleration via the Fermi process at the termination shock of the pulsar wind, magnetic reconnection in the wind, at the termination shock and in the Nebula plays a major role in powering the multi-wavelength signatures of PWNe.Comment: 32 pages, 16 figures, to appear in the book "Modelling Nebulae" edited by D. Torres for Springer, based on the invited contributions to the workshop held in Sant Cugat (Barcelona), June 14-17, 201

A Helicity-Based Method to Infer the CME Magnetic Field Magnitude in Sun and Geospace: Generalization and Extension to Sun-Like and M-Dwarf Stars and Implications for Exoplanet Habitability

Patsourakos et al. (Astrophys. J. 817, 14, 2016) and Patsourakos and Georgoulis (Astron. Astrophys. 595, A121, 2016) introduced a method to infer the axial magnetic field in flux-rope coronal mass ejections (CMEs) in the solar corona and farther away in the interplanetary medium. The method, based on the conservation principle of magnetic helicity, uses the relative magnetic helicity of the solar source region as input estimates, along with the radius and length of the corresponding CME flux rope. The method was initially applied to cylindrical force-free flux ropes, with encouraging results. We hereby extend our framework along two distinct lines. First, we generalize our formalism to several possible flux-rope configurations (linear and nonlinear force-free, non-force-free, spheromak, and torus) to investigate the dependence of the resulting CME axial magnetic field on input parameters and the employed flux-rope configuration. Second, we generalize our framework to both Sun-like and active M-dwarf stars hosting superflares. In a qualitative sense, we find that Earth may not experience severe atmosphere-eroding magnetospheric compression even for eruptive solar superflares with energies ~ 10^4 times higher than those of the largest Geostationary Operational Environmental Satellite (GOES) X-class flares currently observed. In addition, the two recently discovered exoplanets with the highest Earth-similarity index, Kepler 438b and Proxima b, seem to lie in the prohibitive zone of atmospheric erosion due to interplanetary CMEs (ICMEs), except when they possess planetary magnetic fields that are much higher than that of Earth.Comment: http://adsabs.harvard.edu/abs/2017SoPh..292...89

Magnetic Reconnection in Extreme Astrophysical Environments

Magnetic reconnection is a basic plasma process of dramatic rearrangement of magnetic topology, often leading to a violent release of magnetic energy. It is important in magnetic fusion and in space and solar physics --- areas that have so far provided the context for most of reconnection research. Importantly, these environments consist just of electrons and ions and the dissipated energy always stays with the plasma. In contrast, in this paper I introduce a new direction of research, motivated by several important problems in high-energy astrophysics --- reconnection in high energy density (HED) radiative plasmas, where radiation pressure and radiative cooling become dominant factors in the pressure and energy balance. I identify the key processes distinguishing HED reconnection: special-relativistic effects; radiative effects (radiative cooling, radiation pressure, and Compton resistivity); and, at the most extreme end, QED effects, including pair creation. I then discuss the main astrophysical applications --- situations with magnetar-strength fields (exceeding the quantum critical field of about 4 x 10^13 G): giant SGR flares and magnetically-powered central engines and jets of GRBs. Here, magnetic energy density is so high that its dissipation heats the plasma to MeV temperatures. Electron-positron pairs are then copiously produced, making the reconnection layer highly collisional and dressing it in a thick pair coat that traps radiation. The pressure is dominated by radiation and pairs. Yet, radiation diffusion across the layer may be faster than the global Alfv\'en transit time; then, radiative cooling governs the thermodynamics and reconnection becomes a radiative transfer problem, greatly affected by the ultra-strong magnetic field. This overall picture is very different from our traditional picture of reconnection and thus represents a new frontier in reconnection research.Comment: Accepted to Space Science Reviews (special issue on magnetic reconnection). Article is based on an invited review talk at the Yosemite-2010 Workshop on Magnetic Reconnection (Yosemite NP, CA, USA; February 8-12, 2010). 30 pages, no figure

A mathematical framework for critical transitions: normal forms, variance and applications

Critical transitions occur in a wide variety of applications including mathematical biology, climate change, human physiology and economics. Therefore it is highly desirable to find early-warning signs. We show that it is possible to classify critical transitions by using bifurcation theory and normal forms in the singular limit. Based on this elementary classification, we analyze stochastic fluctuations and calculate scaling laws of the variance of stochastic sample paths near critical transitions for fast subsystem bifurcations up to codimension two. The theory is applied to several models: the Stommel-Cessi box model for the thermohaline circulation from geoscience, an epidemic-spreading model on an adaptive network, an activator-inhibitor switch from systems biology, a predator-prey system from ecology and to the Euler buckling problem from classical mechanics. For the Stommel-Cessi model we compare different detrending techniques to calculate early-warning signs. In the epidemics model we show that link densities could be better variables for prediction than population densities. The activator-inhibitor switch demonstrates effects in three time-scale systems and points out that excitable cells and molecular units have information for subthreshold prediction. In the predator-prey model explosive population growth near a codimension two bifurcation is investigated and we show that early-warnings from normal forms can be misleading in this context. In the biomechanical model we demonstrate that early-warning signs for buckling depend crucially on the control strategy near the instability which illustrates the effect of multiplicative noise.Comment: minor corrections to previous versio

Magnetoluminescence

Pulsar Wind Nebulae, Blazars, Gamma Ray Bursts and Magnetars all contain regions where the electromagnetic energy density greatly exceeds the plasma energy density. These sources exhibit dramatic flaring activity where the electromagnetic energy distributed over large volumes, appears to be converted efficiently into high energy particles and gamma-rays. We call this general process magnetoluminescence. Global requirements on the underlying, extreme particle acceleration processes are described and the likely importance of relativistic beaming in enhancing the observed radiation from a flare is emphasized. Recent research on fluid descriptions of unstable electromagnetic configurations are summarized and progress on the associated kinetic simulations that are needed to account for the acceleration and radiation is discussed. Future observational, simulation and experimental opportunities are briefly summarized.Comment: To appear in "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release" of the Space Science Reviews serie