The AIM2 inflammasome is critical for innate immunity to Francisella tularensis.

Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-18. We elucidate here how host macrophages recognize F. tularensis and elicit this proinflammatory response. Using mice deficient in the DNA-sensing inflammasome component AIM2, we demonstrate here that AIM2 is required for sensing F. tularensis. AIM2-deficient mice were extremely susceptible to F. tularensis infection, with greater mortality and bacterial burden than that of wild-type mice. Caspase-1 activation, IL-1beta secretion and cell death were absent in Aim2(-/-) macrophages in response to F. tularensis infection or the presence of cytoplasmic DNA. Our study identifies AIM2 as a crucial sensor of F. tularensis infection and provides genetic proof of its critical role in host innate immunity to intracellular pathogens

Quantum heuristic algorithm for traveling salesman problem

We propose a quantum heuristic algorithm to solve a traveling salesman problem by generalizing Grover search. Sufficient conditions are derived to greatly enhance the probability of finding the tours with extremal costs, reaching almost to unity and they are shown characterized by statistical properties of tour costs. In particular for a Gaussian distribution of the tours along the cost we show that the quantum algorithm exhibits the quadratic speedup of its classical counterpart, similarly to Grover search.Comment: Published versio

Vortex wandering in a forest of splayed columnar defects

We investigate the scaling properties of single flux lines in a random pinning landscape consisting of splayed columnar defects. Such correlated defects can be injected into Type II superconductors by inducing nuclear fission or via direct heavy ion irradiation. The result is often very efficient pinning of the vortices which gives, e.g., a strongly enhanced critical current. The wandering exponent \zeta and the free energy exponent \omega of a single flux line in such a disordered environment are obtained analytically from scaling arguments combined with extreme-value statistics. In contrast to the case of point disorder, where these exponents are universal, we find a dependence of the exponents on details in the probability distribution of the low lying energies of the columnar defects. The analytical results show excellent agreement with numerical transfer matrix calculations in two and three dimensions.Comment: 11 pages, 9 figure

Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3

TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3, which together with MLKL provides both signal 1 and 2 for inflammasome assembly. Cytoplasmic dsRNA activates NLRP3 independent of TRIF, RIPK1, RIPK3 or mitochondrial DRP1, but requires FADD/caspase-8 in wildtype macrophages to remove RIPK3 inhibition. Our study provides a comprehensive analysis of pathways that lead to NLRP3 inflammasome activation in response to dsRNA

DISTANCE ESTIMATION OF CONCEALED OBJECTS WITH STEREOSCOPIC PASSIVE MILLIMETER-WAVE IMAGING

Abstract—Millimeter waves can be used to detect concealed objects because they can penetrate clothing. Therefore, millimeter wave imaging draws increasing attention in security applications for the detection of objects under clothing. In such applications, it is critical to estimate the distances from objects concealed in open spaces. In this paper, we develop a segmentation-based stereo-matching method based on passive millimeter wave imaging to estimate the longitudinal distance from a concealed object. In this method, the concealed object area is segmented and extracted by a k-means algorithm with splitting initialization, which provides an iterative solution for unsupervised learning. The distance from a concealed object is estimated on the basis of discrepancy between corresponding centers of the segmented objects in the image pair. The conventional stereo-matching equation is modified according to the scanning properties of the passive millimeter wave imaging system. We experimentally demonstrate that the proposed method can accurately estimate distances from concealed objects. 1