14,706 research outputs found

    Evolving Bacterial Envelopes and Plasticity of TLR2-Dependent Responses: Basic Research and Translational Opportunities.

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    Innate immune mechanisms that follow early recognition of microbes influence the nature and magnitude of subsequent adaptive immune responses. Early detection of microbes depends on pattern recognition receptors that sense pathogen-associated molecular patterns or microbial-associated molecular patterns (PAMPS or MAMPs, respectively). The bacterial envelope contains MAMPs that include membrane proteins, lipopeptides, glycopolymers, and other pro-inflammatory molecules. Bacteria are selected by environmental pressures resulting in quantitative or qualitative changes in their envelope structures that often promote evasion of host immune responses and therefore, infection. However, recent studies have shown that slight, adaptive changes in MAMPs on the bacterial cell wall may result in their ability to induce the secretion not only of pro-inflammatory cytokines but also of anti-inflammatory cytokines. This effect can fine-tune the subsequent response to microbes expressing these MAMPs and lead to the establishment of a commensal state within the host rather than infectious disease. In this review, we will examine the plasticity of Toll-like receptor (TLR) 2 signaling as evidence of evolving MAMPs, using the better-characterized TLR4 as a template. We will review the role of differential dimerization of TLR2 and the arrangement of signaling complexes and co-receptors in determining the capacity of the host to recognize an array of TLR2 ligands and generate different immune responses to these ligands. Last, we will assess briefly how this plasticity may expand the array of interactions between microbes and immune systems beyond the traditional disease-causing paradigm

    Noncircular rolling joints for vibrational reduction in slewing maneuvers

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    A rolling joint is provided for obtaining slewing maneuvers for various apparatus including space structures, space vehicles, robotic manipulators, and simulators. Two noncircular cylinders, namely a drive and a driven cylinder, are provided in driving contact with one another. This contact is maintained by two pairs of generally S-shaped bands, each pair forming a generally 8-shaped coupling tightly about the circumferential periphery of the noncircular drive and driven cylinders. A stationarily fixed arm extends between and is rotatably journalled with a drive axle and a spindle axle respectively extending through selected rotational points of the drive cylinder and of the driven cylinder. The noncircular cylinders are profiled to obtain the desired varying gear ratio. The novelty of the present invention resides in using specifically profiled noncircular cylinders to obtain a desired varying gear ratio

    Detection of Early-Stage Enterprise Infection by Mining Large-Scale Log Data

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    Recent years have seen the rise of more sophisticated attacks including advanced persistent threats (APTs) which pose severe risks to organizations and governments by targeting confidential proprietary information. Additionally, new malware strains are appearing at a higher rate than ever before. Since many of these malware are designed to evade existing security products, traditional defenses deployed by most enterprises today, e.g., anti-virus, firewalls, intrusion detection systems, often fail at detecting infections at an early stage. We address the problem of detecting early-stage infection in an enterprise setting by proposing a new framework based on belief propagation inspired from graph theory. Belief propagation can be used either with "seeds" of compromised hosts or malicious domains (provided by the enterprise security operation center -- SOC) or without any seeds. In the latter case we develop a detector of C&C communication particularly tailored to enterprises which can detect a stealthy compromise of only a single host communicating with the C&C server. We demonstrate that our techniques perform well on detecting enterprise infections. We achieve high accuracy with low false detection and false negative rates on two months of anonymized DNS logs released by Los Alamos National Lab (LANL), which include APT infection attacks simulated by LANL domain experts. We also apply our algorithms to 38TB of real-world web proxy logs collected at the border of a large enterprise. Through careful manual investigation in collaboration with the enterprise SOC, we show that our techniques identified hundreds of malicious domains overlooked by state-of-the-art security products

    Thomson backscattering in combined two laser and magnetic field

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    The Thomson backscattering of an electron moving in combined fields is studied by a dynamically assisted mechanism. The combined fields are composed of two co-propagating laser fields and a magnetic field, where the first laser field is strong and low-frequency while the second is weak and high-frequency, relatively. The dependence of fundamental frequency of emission on the ratio of incident laser high-to-low frequency is presented and the spectrum of backscattering is obtained. It is found that, with a magnetic field, the peak of the spectrum and the corresponding radiation frequency are significantly larger in case of two-laser than that in case of only one laser. They are also improved obviously as the frequency of the weak laser field. Another finding is the nonlinear correlation between the emission intensity of the backscattering and the intensity of the weak laser field. These results provide a new possibility to adjust and control the spectrum by changing the ratios of frequency and intensity of the two laser fields.Comment: 13 pages, 4 figure
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