Biofilms are complex communities of bacteria encased in a matrix composed primarily of polysaccharides, extracellular DNA, and protein. Staphylococcus aureus (S. aureus) can form biofilm infections, which are often debilitating due to their chronicity and recalcitrance to antibiotic therapy. Currently, the immune mechanisms elicited during biofilm growth and their impact on bacterial clearance remains to be defined. We utilized a mouse model of catheter-associated biofilm infection to assess the functional importance of Toll-like receptors 2 and 9 in the host immune response during biofilm formation, since ligands for both receptors are present within the biofilm. Interestingly, neither receptor impacted bacterial density or inflammatory mediator secretion during biofilm growth in vivo, suggesting that S. aureus biofilms circumvent these traditional bacterial recognition pathways. Several potential mechanisms were identified to account for biofilm evasion of innate immunity, including significant reductions in IL-1β, TNF-α, CXCL2, and CCL2 expression during biofilm infection compared to the wound healing response elicited by sterile catheters, limited macrophage invasion into biofilms in vivo, and a skewing of the immune response away from a microbicidal phenotype as evidenced by decreases in iNOS expression concomitant with robust arginase-1 induction. Co-culture studies of macrophages with S. aureus biofilms in vitro revealed that macrophages successful at biofilm invasion displayed limited phagocytosis and gene expression patterns reminiscent of alternatively activated M2 macrophages. Collectively, these findings demonstrate that S. aureus biofilms are capable of attenuating traditional host proinflammatory responses, which may explain why biofilm infections persist in an immunocompetent host.

Abstract. Secure multi-party computation has been considered by the cryptographic community for a number of years. Until recently it has been a purely theoretical area, with few implementations with which to test various ideas. This has led to a number of optimisations being proposed which are quite restricted in their application. In this paper we describe an implementation of the two-party case, using Yao's garbled circuits, and present various algorithmic protocol improvements. These optimisations are analysed both theoretically and empirically, using experiments of various adversarial situations. Our experimental data is provided for reasonably large circuits, including one which performs an AES encryption, a problem which we discuss in the context of various possible applications.

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Anthracyclines are valuable cytotoxic agents in cancer treatment. However, their usefulness is limited by cumulative dose-dependent cardiotoxicity that may manifest as life-threatening congestive heart failure. To avoid cardiotoxicity, the use of doxorubicin is typically capped at a safe cumulative dose. Liposomal formulations may reduce cardiac risks whilst maintaining anti-cancer efficacy. Efficacy and safety studies of non-pegylated liposomal doxorubicin (NPLD) in metastatic breast cancer (MBC) are reviewed, along with studies that examine efficacy and cardiac tolerability in combination with newer agents such as paclitaxel and trastuzumab. These show that cardiac safety of liposomal doxorubicin is similar to that of epirubicin in cumulative dose, but that the formulation, unlike epirubicin, has similar anti-cancer efficacy to doxorubicin at equimolar doses. Liposomal doxorubicin may have a better therapeutic index than non-liposomal anthracyclines. This justifies further studies in patients where cumulative cardiotoxicity is a concern, as does study of its use with other potentially cardiotoxic agents.

In this paper we examine composability properties for the fundamental task of key exchange. Roughly speaking, we show that key exchange protocols secure in the prevalent model of Bellare and Rogaway can be composed with arbitrary protocols that require symmetrically distributed keys. This composition theorem holds if the key exchange protocol satisfies an additional technical requirement that our analysis brings to light: it should be possible to determine which sessions derive equal keys given only the publicly available information. What distinguishes our results from virtually all existing work is that we do not rely, neither directly nor indirectly, on the simulation paradigm. Instead, our security notions and composition theorems exclusively use a game-based formalism. We thus avoid several undesirable consequences of simulation-based security notions and support applicability to a broader class of protocols. In particular, we offer an abstract formalization of game-based security that should be of independent interest in other investigations using gamebased formalisms.