Tree-Level Stability Without Spacetime Fermions: Novel Examples in String Theory

Is perturbative stability intimately tied with the existence of spacetime fermions in string theory in more than two dimensions? Type 0'B string theory in ten-dimensional flat space is a rare example of a non-tachyonic, non-supersymmetric string theory with a purely bosonic closed string spectrum. However, all known type 0' constructions exhibit massless NSNS tadpoles signaling the fact that we are not expanding around a true vacuum of the theory. In this note, we are searching for perturbatively stable examples of type 0' string theory without massless tadpoles in backgrounds with a spatially varying dilaton. We present two examples with this property in non-critical string theories that exhibit four- and six-dimensional Poincare invariance. We discuss the D-branes that can be embedded in this context and the type of gauge theories that can be constructed in this manner. We also comment on the embedding of these non-critical models in critical string theories and their holographic (Little String Theory) interpretation and propose a general conjecture for the role of asymptotic supersymmetry in perturbative string theory.Comment: harvmac, 29 pages; v2 minor changes, version to appear in JHE

Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

Natural Killer Cell Signal Integration Balances Synapse Symmetry and Migration

Imaging immune surveillance by natural killer (NK) cells has revealed that integration of activating and inhibitory signals determines whether or not NK cells stop to kill the target cell or retain a migratory configuration

Forage base and megafauna restoration in the “Krasny bor” nature reserve

Forage base is a key concept in the matter of specific and numeric composition reconstruction of large herbivores. In researches the forage base of “Krasny Bor” nature reserve was estimated. Now there is a restoration of red deer and bison species there. The assess ment of forage amount indicated their rather small quantity, in particular concerning woody forages. Comparison of the established for-age reserve with their potential amount of intake by the large herbivorous testifies that forage reserves in the course of hoofed animals activity will steadily decrease. Low forage efficiency of nature reserve forests first of all is defined by features of the studied forest ecosystems located in a subzone of the South Taiga. In the future for highly productive heterogeneous forest ecosystems reconstruction it will be necessary to recreate all food chains, including restoration of grazing chains by introduction of graz-ing species of large herbivores

Vav1 Dephosphorylation by the Tyrosine Phosphatase SHP-1 as a Mechanism for Inhibition of Cellular Cytotoxicity

Here, we present data suggesting a novel mechanism for regulation of natural killer (NK) cell cytotoxicity through inhibitory receptors. Interaction of activation receptors with their ligands on target cells induces cytotoxicity by NK cells. This activation is under negative control by inhibitory receptors that recruit tyrosine phosphatase SHP-1 upon binding major histocompatibility class I on target cells. How SHP-1 blocks the activation pathway is not known. To identify SHP-1 substrates, an HLA-C-specific inhibitory receptor fused to a substrate-trapping mutant of SHP-1 was expressed in NK cells. Phosphorylated Vav1, a regulator of actin cytoskeleton, was the only protein detectably associated with the catalytic site of SHP-1 during NK cell contact with target cells expressing HLA-C. Vav1 trapping was independent of actin polymerization, suggesting that inhibition of cellular cytotoxicity occurs through an early dephosphorylation of Vav1 by SHP-1, which blocks actin-dependent activation signals. Such a mechanism explains how inhibitory receptors can block activating signals induced by different receptors

Boltzmann energy-based image analysis demonstrates that extracellular domain size differences explain protein segregation at immune synapses

Immune synapses formed by T and NK cells both show segregation of the integrin ICAM1 from other proteins such as CD2 (T cell) or KIR (NK cell). However, the mechanism by which these proteins segregate remains unclear; one key hypothesis is a redistribution based on protein size. Simulations of this mechanism qualitatively reproduce observed segregation patterns, but only in certain parameter regimes. Verifying that these parameter constraints in fact hold has not been possible to date, this requiring a quantitative coupling of theory to experimental data. Here, we address this challenge, developing a new methodology for analysing and quantifying image data and its integration with biophysical models. Specifically we fit a binding kinetics model to 2 colour fluorescence data for cytoskeleton independent synapses (2 and 3D) and test whether the observed inverse correlation between fluorophores conforms to size dependent exclusion, and further, whether patterned states are predicted when model parameters are estimated on individual synapses. All synapses analysed satisfy these conditions demonstrating that the mechanisms of protein redistribution have identifiable signatures in their spatial patterns. We conclude that energy processes implicit in protein size based segregation can drive the patternation observed in individual synapses, at least for the specific examples tested, such that no additional processes need to be invoked. This implies that biophysical processes within the membrane interface have a crucial impact on cell:cell communication and cell signalling, governing protein interactions and protein aggregation