Active and Passive Immunization Protects against Lethal, Extreme Drug Resistant-Acinetobacter baumannii Infection

Extreme-drug-resistant (XDR) Acinetobacter baumannii is a rapidly emerging pathogen causing infections with unacceptably high mortality rates due to inadequate available treatment. New methods to prevent and treat such infections are a critical unmet medical need. To conduct a rational vaccine discovery program, OmpA was identified as the primary target of humoral immune response after intravenous infection by A. baumannii in mice. OmpA was >99% conserved at the amino acid level across clinical isolates harvested between 1951 and 2009 from cerebrospinal fluid, blood, lung, and wound infections, including carbapenem-resistant isolates, and was ≥89% conserved among other sequenced strains, but had minimal homology to the human proteome. Vaccination of diabetic mice with recombinant OmpA (rOmpA) with aluminum hydroxide adjuvant markedly improved survival and reduced tissue bacterial burden in mice infected intravenously. Vaccination induced high titers of anti-OmpA antibodies, the levels of which correlated with survival in mice. Passive transfer with immune sera recapitulated protection. Immune sera did not enhance complement-mediated killing but did enhance opsonophagocytic killing of A. baumannii. These results define active and passive immunization strategies to prevent and treat highly lethal, XDR A. baumannii infections

Network positioning from the edge: an empirical study of the effectiveness of network positioning in P2P systems

Abstract—Network positioning systems provide an important service to large-scale P2P systems, potentially enabling clients to achieve higher performance, reduce cross-ISP traffic and improve the robustness of the system to failures. Because traces representative of this environment are generally unavailable, and there is no platform suited for experimentation at the appropriate scale, network positioning systems have been commonly implemented and evaluated in simulation and on research testbeds. The performance of network positioning remains an open question for large deployments at the edges of the network. This paper evaluates how four key classes of network positioning systems fare when deployed at scale and measured in P2P systems where they are used. Using 2 billion network measurements gathered from more than 43,000 IP addresses probing over 8 million other IPs worldwide, we show that network positioning exhibits noticeably worse performance than previously reported in studies conducted on research testbeds. To explain this result, we identify several key properties of this environment that call into question fundamental assumptions driving network positioning research. I

Drafting behind akamai (travelocity-based detouring

To enhance web browsing experiences, content distribution networks (CDNs) move web content “closer ” to clients by caching copies of web objects on thousands of servers worldwide. Additionally, to minimize client download times, such systems perform extensive network and server measurements, and use them to redirect clients to different servers over short time scales. In this paper, we explore techniques for inferring and exploiting network measurements performed by the largest CDN, Akamai; our objective is to locate and utilize quality Internet paths without performing extensive path probing or monitoring. Our contributions are threefold. First, we conduct a broad measurement study of Akamai’s CDN. We probe Akamai’s network from 140 PlanetLab vantage points for two months. We find that Akamai redirection times, while slightly higher than advertised, ar

Relative Network Positioning via CDN Redirections

Abstract—Many large-scale distributed systems can benefit from a service that allows them to select among alternative nodes based on their relative network positions. A variety of approaches propose new measurement infrastructures that attempt to scale this service to large numbers of nodes by reducing the amount of direct measurements to end hosts. In this paper, we introduce a new approach to relative network positioning that eliminates direct probing by leveraging pre-existing infrastructure. Specif-ically, we exploit the dynamic association of nodes with replica servers from large content distribution networks (CDNs) to deter-mine relative position information – we call this approach CDN-based Relative network Positioning (CRP). We demonstrate how CRP can support two common examples of location information used by distributed applications: server selection and dynamic node clustering. After describing CRP in detail, we present results from an extensive wide-area evaluation that demonstrates its effectiveness