Syk-dependent Phosphorylation of CLEC-2: A Novel Mechanism of Hem-Immunoreceptor Tyrosine-Based Activation Motif Signaling

The C-type lectin-like receptor CLEC-2 signals via phosphorylation of a single cytoplasmic YXXL sequence known as a hem-immunoreceptor tyrosine-based activation motif (hemITAM). In this study, we show that phosphorylation of CLEC-2 by the snake toxin rhodocytin is abolished in the absence of the tyrosine kinase Syk but is not altered in the absence of the major platelet Src family kinases, Fyn, Lyn, and Src, or the tyrosine phosphatase CD148, which regulates the basal activity of Src family kinases. Further, phosphorylation of CLEC-2 by rhodocytin is not altered in the presence of the Src family kinase inhibitor PP2, even though PLCγ2 phosphorylation and platelet activation are abolished. A similar dependence of phosphorylation of CLEC-2 on Syk is also seen in response to stimulation by an IgG mAb to CLEC-2, although interestingly CLEC-2 phosphorylation is also reduced in the absence of Lyn. These results provide the first definitive evidence that Syk mediates phosphorylation of the CLEC-2 hemITAM receptor with Src family kinases playing a critical role further downstream through the regulation of Syk and other effector proteins, providing a new paradigm in signaling by YXXL-containing receptors

Denoising Autoencoders for fast Combinatorial Black Box Optimization

Estimation of Distribution Algorithms (EDAs) require flexible probability models that can be efficiently learned and sampled. Autoencoders (AE) are generative stochastic networks with these desired properties. We integrate a special type of AE, the Denoising Autoencoder (DAE), into an EDA and evaluate the performance of DAE-EDA on several combinatorial optimization problems with a single objective. We asses the number of fitness evaluations as well as the required CPU times. We compare the results to the performance to the Bayesian Optimization Algorithm (BOA) and RBM-EDA, another EDA which is based on a generative neural network which has proven competitive with BOA. For the considered problem instances, DAE-EDA is considerably faster than BOA and RBM-EDA, sometimes by orders of magnitude. The number of fitness evaluations is higher than for BOA, but competitive with RBM-EDA. These results show that DAEs can be useful tools for problems with low but non-negligible fitness evaluation costs.Comment: corrected typos and small inconsistencie

Dynamical decompactification from brane gases in eleven-dimensional supergravity

Brane gas cosmology provides a dynamical decompactification mechanism that could account for the number of spacetime dimensions we observe today. In this work we discuss this scenario taking into account the full bosonic sector of eleven-dimensional supergravity. We find new cosmological solutions that can dynamically explain the existence of three large spatial dimensions characterised by an universal asymptotic scaling behaviour and a large number of initially unwrapped dimensions. This type of solutions enlarge the possible initial conditions of the Universe in the Hagedorn phase and consequently can potentially increase the probability of dynamical decompactification from anisotropically wrapped backgrounds.Comment: 8 figures, JHEP3 styl

Self-assembling DNA-caged particles: nanoblocks for hierarchical self-assembly

DNA is an ideal candidate to organize matter on the nanoscale, primarily due to the specificity and complexity of DNA based interactions. Recent advances in this direction include the self-assembly of colloidal crystals using DNA grafted particles. In this article we theoretically study the self-assembly of DNA-caged particles. These nanoblocks combine DNA grafted particles with more complicated purely DNA based constructs. Geometrically the nanoblock is a sphere (DNA grafted particle) inscribed inside a polyhedron (DNA cage). The faces of the DNA cage are open, and the edges are made from double stranded DNA. The cage vertices are modified DNA junctions. We calculate the equilibriuim yield of self-assembled, tetrahedrally caged particles, and discuss their stability with respect to alternative structures. The experimental feasability of the method is discussed. To conclude we indicate the usefulness of DNA-caged particles as nanoblocks in a hierarchical self-assembly strategy.Comment: v2: 21 pages, 8 figures; revised discussion in Sec. 2, replaced 2 figures, added new reference

Contrasting Energy Scales of the Reentrant Integer Quantum Hall States

We report drastically different onset temperatures of the reentrant integer quantum Hall states in the second and third Landau level. This finding is in quantitative disagreement with the Hartree-Fock theory of the bubble phases which is thought to describe these reentrant states. Our results indicate that the number of electrons per bubble in either the second or the third Landau level is likely different than predicted

Bumps and rings in a two-dimensional neural field: splitting and rotational instabilities

In this paper we consider instabilities of localised solutions in planar neural field firing rate models of Wilson-Cowan or Amari type. Importantly we show that angular perturbations can destabilise spatially localised solutions. For a scalar model with Heaviside firing rate function we calculate symmetric one-bump and ring solutions explicitly and use an Evans function approach to predict the point of instability and the shapes of the dominant growing modes. Our predictions are shown to be in excellent agreement with direct numerical simulations. Moreover, beyond the instability our simulations demonstrate the emergence of multi-bump and labyrinthine patterns. With the addition of spike-frequency adaptation, numerical simulations of the resulting vector model show that it is possible for structures without rotational symmetry, and in particular multi-bumps, to undergo an instability to a rotating wave. We use a general argument, valid for smooth firing rate functions, to establish the conditions necessary to generate such a rotational instability. Numerical continuation of the rotating wave is used to quantify the emergent angular velocity as a bifurcation parameter is varied. Wave stability is found via the numerical evaluation of an associated eigenvalue problem

Analytic structure of radiation boundary kernels for blackhole perturbations

Exact outer boundary conditions for gravitational perturbations of the Schwarzschild metric feature integral convolution between a time-domain boundary kernel and each radiative mode of the perturbation. For both axial (Regge-Wheeler) and polar (Zerilli) perturbations, we study the Laplace transform of such kernels as an analytic function of (dimensionless) Laplace frequency. We present numerical evidence indicating that each such frequency-domain boundary kernel admits a "sum-of-poles" representation. Our work has been inspired by Alpert, Greengard, and Hagstrom's analysis of nonreflecting boundary conditions for the ordinary scalar wave equation.Comment: revtex4, 14 pages, 12 figures, 3 table