T cell renewal rates, telomerase, and telomere length shortening

Measurements on the average telomere lengths of normal human naive and memory T cells suggested that 1) naive and memory human T cells have similar division rates, and 2) that the difference between naive and memory cells reflects the degree of clonal expansion during normal immune reactions. Here we develop mathematic models describing how the population average of telomere length depends on the cell division rates of naive and memory T cells during clonal expansion and normal renewal. The results show that 1) telomeres shorten with twice the cell division rate, 2) that the conventional approach of estimating telomere length shortening per mean population doubling gives rise to estimates that are 39% larger than the "true" loss per cell division, 3) that naive and memory T cells are expected to shorten their telomeres at rates set by the division rate of the naive T cells only, i.e., irrespective of the division rate of memory T cells, 4) that the measured difference in the average telomere length between naive and memory T cells may largely reflect the difference in renewal rates between these subpopulations rather than the clonal expansion, and 5) that full telomerase compensation during clonal expansion is consistent with all data on the shortening of telomere length in, and between, naive and memory T cells. Thus we reconcile the apparent contradictions between the demonstrated difference in division rates between human naive and memory T cells and their similar rates of telomere shortening, and the demonstrated telomere shortening in the presence of telomerase activity

How Specific Should Immunological Memory Be?

Protection against infection hinges on a close interplay between the innate immune system and the adaptive immune system. Depending on the type and context of a pathogen, the innate system instructs the adaptive immune system to induce an appropriate immune response. Here, we hypothesize that the adaptive immune system stores these instructions by changing from a naive to an appropriate memory phenotype. In a secondary immune reaction, memory lymphocytes adhere to their instructed phenotype. Because cross-reactions with unrelated Ags can be detrimental, such a qualitative form of memory requires a sufficient degree of specificity of the adaptive immune system. For example, lymphocytes instructed to clear a particular pathogen may cause autoimmunity when cross-reacting with ignored self molecules. Alternatively, memory cells may induce an immune response of the wrong mode when cross-reacting with subsequent pathogens. To maximize the likelihood of responding to a wide variety of pathogens, it is also required that the immune system be sufficiently cross-reactive. By means of a probabilistic model, we show that these conflicting requirements are met optimally by a highly specific memory lymphocyte repertoire. This explains why the lymphocyte system that was built on a preserved functional innate immune system has such a high degree of specificity. Our analysis suggests that 1) memory lymphocytes should be more specific than naive lymphocytes and 2) species with small lymphocyte repertoires should be more vulnerable to both infection and autoimmune diseases

Occlusion-related lateral connections stabilize kinetic depth stimuli through perceptual coupling

Local sensory information is often ambiguous forcing the brain to integrate spatiotemporally separated information for stable conscious perception. Lateral connections between clusters of similarly tuned neurons in the visual cortex are a potential neural substrate for the coupling of spatially separated visual information. Ecological optics suggests that perceptual coupling of visual information is particularly beneficial in occlusion situations. Here we present a novel neural network model and a series of human psychophysical experiments that can together explain the perceptual coupling of kinetic depth stimuli with activity-driven lateral information sharing in the far depth plane. Our most striking finding is the perceptual coupling of an ambiguous kinetic depth cylinder with a coaxially presented and disparity defined cylinder backside, while a similar frontside fails to evoke coupling. Altogether, our findings are consistent with the idea that clusters of similarly tuned far depth neurons share spatially separated motion information in order to resolve local perceptual ambiguities. The classification of far depth in the facilitation mechanism results from a combination of absolute and relative depth that suggests a functional role of these lateral connections in the perception of partially occluded objects

Critical Dynamics of the Contact Process with Quenched Disorder

We study critical spreading dynamics in the two-dimensional contact process (CP) with quenched disorder in the form of random dilution. In the pure model, spreading from a single particle at the critical point $\lambda_c$ is characterized by the critical exponents of directed percolation: in $2+1$ dimensions, $\delta = 0.46$, $\eta = 0.214$, and $z = 1.13$. Disorder causes a dramatic change in the critical exponents, to $\delta \simeq 0.60$, $\eta \simeq -0.42$, and $z \simeq 0.24$. These exponents govern spreading following a long crossover period. The usual hyperscaling relation, $4 \delta + 2 \eta = d z$, is violated. Our results support the conjecture by Bramson, Durrett, and Schonmann [Ann. Prob. {\bf 19}, 960 (1991)], that in two or more dimensions the disordered CP has only a single phase transition.Comment: 11 pages, REVTeX, four figures available on reques

Self-Organized Critical Directed Percolation

We introduce and study a dynamic transport model exhibiting Self-Organized Criticality. The novel concepts of our model are the probabilistic propagation of activity and unbiased random repartition of energy among the active site and its nearest neighbors. For space dimensionality $d\geq 2$ we argue that the model is related to $d+1$ dimensional directed percolation, with time interpreted as the preferred direction.Comment: 4 two-column pages (revtex), 3 ps figures included with epsf, g-zipped, uuencode

Study of the multi-species annihilating random walk transition at zero branching rate - cluster scaling behavior in a spin model

Numerical and theoretical studies of a one-dimensional spin model with locally broken spin symmetry are presented. The multi-species annihilating random walk transition found at zero branching rate previously is investigated now concerning the cluster behaviour of the underlying spins. Generic power law behaviors are found, besides the phase transition point, also in the active phase with fulfillment of the hyperscaling law. On the other hand scaling laws connecting bulk- and cluster exponents are broken - a possibility in no contradiction with basic scaling assumptions because of the missing absorbing phase.Comment: 7 pages, 6 figures, final form to appear in PRE Nov.200

Generalized contact process on random environments

Spreading from a seed is studied by Monte Carlo simulation on a square lattice with two types of sites affecting the rates of birth and death. These systems exhibit a critical transition between survival and extinction. For time- dependent background, this transition is equivalent to those found in homogeneous systems (i.e. to directed percolation). For frozen backgrounds, the appearance of Griffiths phase prevents the accurate analysis of this transition. For long times in the subcritical region, spreading remains localized in compact (rather than ramified) patches, and the average number of occupied sites increases logarithmically in the surviving trials.Comment: 6 pages, 7 figure

Investigations on nano- and submicron-particle generation by spray painting processes

[EN] This paper presents experimental and numerical studies to determine the particle size distributions (PSD) and concentrations in paint overspray. Two kinds of paint materials, solvent borne and water borne paints, both with and without manufactured nanomaterials (pigments), and an industrial spray gun were used. Different aerosol measuring techniques, namely the Spraytec Fraunhofer type particle sizer for micro-sized droplets in the spray jet and the Scanning Mobility Particle Sizer (SMPS) for nano particles in paint overspray were applied. It was found, that solvent borne clear coats create significantly higher number concentration of nano-sized droplets than the water borneprimers. Only small differences in PSD between paints with and without manufactured nanomaterials were found. Numerical simulations of droplet trajectories within the spray booth, for both micro and nano sized droplets, were carried out. Based on the experimental and numerical results, a representative particle size distribution (smaller than 1 μm) for the given spray gun was obtained. Effects of turbulence models on the particle deposition on targets, especially for submicron particles, have been analysed in detailed.The present investigations have been supported by Verkehr, Innovation und Technologie, Austria (BMVIT) and Fraunhofer Society in Germany within a European joint research project NanoGeCo. This support is gratefully acknowledged by the authors.Ye, Q.; Tiedje, O.; Srinivas, SR.; Noest, T.; Uhrner, U. (2017). Investigations on nano- and submicron-particle generation by spray painting processes. En Ilass Europe. 28th european conference on Liquid Atomization and Spray Systems. Editorial Universitat Politècnica de València. 122-129. https://doi.org/10.4995/ILASS2017.2017.4666OCS12212

Visual consciousness: the binocular rivalry explosion

A new behavioural technique solves a long-standing puzzle of binocular suppression, demonstrating that adapting reciprocal inhibition governs visual sensitivity, and raising key questions about visual awareness

Multi-Timescale Perceptual History Resolves Visual Ambiguity

When visual input is inconclusive, does previous experience aid the visual system in attaining an accurate perceptual interpretation? Prolonged viewing of a visually ambiguous stimulus causes perception to alternate between conflicting interpretations. When viewed intermittently, however, ambiguous stimuli tend to evoke the same percept on many consecutive presentations. This perceptual stabilization has been suggested to reflect persistence of the most recent percept throughout the blank that separates two presentations. Here we show that the memory trace that causes stabilization reflects not just the latest percept, but perception during a much longer period. That is, the choice between competing percepts at stimulus reappearance is determined by an elaborate history of prior perception. Specifically, we demonstrate a seconds-long influence of the latest percept, as well as a more persistent influence based on the relative proportion of dominance during a preceding period of at least one minute. In case short-term perceptual history and long-term perceptual history are opposed (because perception has recently switched after prolonged stabilization), the long-term influence recovers after the effect of the latest percept has worn off, indicating independence between time scales. We accommodate these results by adding two positive adaptation terms, one with a short time constant and one with a long time constant, to a standard model of perceptual switching