Low Ligand Requirement for Deletion and Lack of Synapses in Positive Selection Enforce the Gauntlet of Thymic T Cell Maturation

SummaryImmature double-positive (CD4+CD8+) thymocytes respond to negatively selecting peptide-MHC ligands by forming an immune synapse that sustains contact with the antigen-presenting cell (APC). Using fluorescently labeled peptides, we showed that as few as two agonist ligands could promote APC contact and subsequent apoptosis in reactive thymocytes. Furthermore, we showed that productive signaling for positive selection, as gauged by nuclear translocation of a green fluorescent protein (GFP)-labeled NFATc construct, did not involve formation of a synapse between thymocytes and selecting epithelial cells in reaggregate thymus cultures. Antibody blockade of endogenous positively selecting ligands prevented NFAT nuclear accumulation in such cultures and reversed NFAT accumulation in previously stimulated thymocytes. Together, these data suggest a “gauntlet” model in which thymocytes mature by continually acquiring and reacquiring positively selecting signals without sustained contact with epithelial cells, thereby allowing them to sample many cell surfaces for potentially negatively selecting ligands

Imaging Synapse Formation during Thymocyte Selection Inability of CD3ζ to Form a Stable Central Accumulation during Negative Selection

AbstractTCR signaling can result in cell fates ranging from activation to tolerance to apoptosis. Organization of molecules in an “immunological synapse” between mature T cells and APCs correlates with the strength of TCR signaling. To investigate synapse formation during thymic selection, we have established a reaggregate system in which molecular recruitment of GFP fusion proteins to thymocyte:stromal cell interfaces can be visualized in real time. We demonstrate that negative selection is associated with efficient conjugate formation and rapid recruitment of p56lck and CD3ζ to an immunological synapse. Interestingly, CD3ζ-GFP does not accumulate at the center of the synapse, as in mature T cells, but at the periphery across a wide range of ligand densities. This implicates differences in synapse geometry in initiation of alternate signals downstream of the TCR

Heavy--light mesons in a bilocal effective theory

Heavy--light mesons are described in an effective quark theory with a two--body vector--type interaction. The bilocal interaction is taken to be instantaneous in the rest frame of the bound state, but formulated covariantly through the use of a boost vector. The chiral symmetry of the light flavor is broken spontaneously at mean field level. The framework for our discussion of bound states is the effective bilocal meson action obtained by bosonization of the quark theory. Mesons are described by 3--dimensional wave functions satisfying Salpeter equations, which exhibit both Goldstone solutions in the chiral limit and heavy--quark symmetry for $m_Q\rightarrow\infty$. We present numerical solutions for pseudoscalar $D$-- and $B$--mesons. Heavy--light meson spectra and decay constants are seen to be sensitive to the description of chiral symmetry breaking (dynamically generated vs.\ constant quark mass).Comment: (34 p., standard LaTeX, 7 PostScript figures appended) UNITUE-THEP-17/9

A progressive refinement approach for the visualisation of implicit surfaces

Visualising implicit surfaces with the ray casting method is a slow procedure. The design cycle of a new implicit surface is, therefore, fraught with long latency times as a user must wait for the surface to be rendered before being able to decide what changes should be introduced in the next iteration. In this paper, we present an attempt at reducing the design cycle of an implicit surface modeler by introducing a progressive refinement rendering approach to the visualisation of implicit surfaces. This progressive refinement renderer provides a quick previewing facility. It first displays a low quality estimate of what the final rendering is going to be and, as the computation progresses, increases the quality of this estimate at a steady rate. The progressive refinement algorithm is based on the adaptive subdivision of the viewing frustrum into smaller cells. An estimate for the variation of the implicit function inside each cell is obtained with an affine arithmetic range estimation technique. Overall, we show that our progressive refinement approach not only provides the user with visual feedback as the rendering advances but is also capable of completing the image faster than a conventional implicit surface rendering algorithm based on ray casting

Matrix theory of gravitation

A new classical theory of gravitation within the framework of general relativity is presented. It is based on a matrix formulation of four-dimensional Riemann-spaces and uses no artificial fields or adjustable parameters. The geometrical stress-energy tensor is derived from a matrix-trace Lagrangian, which is not equivalent to the curvature scalar R. To enable a direct comparison with the Einstein-theory a tetrad formalism is utilized, which shows similarities to teleparallel gravitation theories, but uses complex tetrads. Matrix theory might solve a 27-year-old, fundamental problem of those theories (sec. 4.1). For the standard test cases (PPN scheme, Schwarzschild-solution) no differences to the Einstein-theory are found. However, the matrix theory exhibits novel, interesting vacuum solutions.Comment: 24 page

Lorentz violation and the proper-time method

In this paper, we apply the proper-time method to generate the Lorentz-violating Chern-Simons terms in the four-dimensional Yang-Mills and non-linearized gravity theories. It is shown that the coefficient of the induced Chern-Simons term is finite but regularization dependent.Comment: 11 pages, Revtex

Effective chiral lagrangian in the chiral limit from the instanton vacuum

We study the effective chiral Lagrangian in the chiral limit from the instanton vacuum. Starting from the nonlocal effective chiral action, we derive the effective chiral Lagrangian, using the derivative expansion to order $O(p^4)$ in the chiral limit. The low energy constants, $L_1$, $L_2$, and $L_3$ are determined and compared with various models and the corresponding empirical data. The results are in a good agreement with the data. We also discuss about the upper limit of the sigma meson, based on the present results.Comment: 14 pages, 5 figures, submitted to Phys.Rev.

Analysis of the doubly heavy baryons in the nuclear matter with the QCD sum rules

In this article, we study the doubly heavy baryon states $\Xi_{cc}$, $\Omega_{cc}$, $\Xi_{bb}$ and $\Omega_{bb}$ in the nuclear matter using the QCD sum rules, and derive three coupled QCD sum rules for the masses, vector self-energies and pole residues. The predictions for the mass-shifts in the nuclear matter $\Delta M_{\Xi_{cc}}=-1.11\,\rm{GeV}$, $\Delta M_{\Omega_{cc}}=-0.33\,\rm{GeV}$, $\Delta M_{\Xi_{bb}}=-3.37\,\rm{GeV}$ and $\Delta M_{\Omega_{bb}}=-1.05\,\rm{GeV}$ can be confronted with the experimental data in the future.Comment: 10 pages, 4 figure

Masses of ground and excited-state hadrons

We present the first Dyson-Schwinger equation calculation of the light hadron spectrum that simultaneously correlates the masses of meson and baryon ground- and excited-states within a single framework. At the core of our analysis is a symmetry-preserving treatment of a vector-vector contact interaction. In comparison with relevant quantities the root-mean-square-relative-error/degree-of freedom is 13%. Notable amongst our results is agreement between the computed baryon masses and the bare masses employed in modern dynamical coupled-channels models of pion-nucleon reactions. Our analysis provides insight into numerous aspects of baryon structure; e.g., relationships between the nucleon and Delta masses and those of the dressed-quark and diquark correlations they contain.Comment: 25 pages, 7 figures, 4 table