8 research outputs found

    Studies on the physics and chemistry of estuarine waters In Chesapeake Bay

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    Estuarine waters are understood to be those water masses which by virtue of their position are directly subject to the combined action of river and tidal currents. They may be considered to reflect certain dominant forces as well as progressive trends that determine their individualistic though changing hydrographic as well as biologic properties. The factors that lend individuality to these bodies may exhibit profound differences in different latitudes and yet, in certain fundamental respects, the waters possess important characteristics in common...

    Communications Biophysics

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    Contains research objectives and summary of research on thirteen research projects split into four section.National Institutes of Health (Grant 1 RO1 NS10737-01)National Institutes of Health (Grant 1 ROI NS10916-01)National Institutes of Health (Grant 5 RO1 NS11000-02)National Institutes of Health (Grant 1 RO1 NS11153-01)Harvard M.I.T. Rehabilitation Engineering CenterU. S. Department of Health, Education, and Welfare, Grant 23-P-55854National Institutes of Health (Grant 1 RO1 NS11680-01)Norlin Music, Inc.Clarence J. LeBel FundNational Institutes of Health (Grant 1 RO1 NS11080-01A1)National Institutes of Health (Grant 5 TO1 GM01555-08)M.I.T. Health Sciences FundBoston City Hospital Purchase Order 1176-05-21335-C

    The Pore-Forming Toxin Listeriolysin O Mediates a Novel Entry Pathway of L. monocytogenes into Human Hepatocytes

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    Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin listeriolysin O (LLO) facilitates bacterial escape from the internalization vesicle into the cytoplasm, where bacteria divide and undergo cell-to-cell spreading via actin-based motility. In the present study we demonstrate that in addition to InlA and InlB, LLO is required for efficient internalization of L. monocytogenes into human hepatocytes (HepG2). Surprisingly, LLO is an invasion factor sufficient to induce the internalization of noninvasive Listeria innocua or polystyrene beads into host cells in a dose-dependent fashion and at the concentrations produced by L. monocytogenes. To elucidate the mechanisms underlying LLO-induced bacterial entry, we constructed novel LLO derivatives locked at different stages of the toxin assembly on host membranes. We found that LLO-induced bacterial or bead entry only occurs upon LLO pore formation. Scanning electron and fluorescence microscopy studies show that LLO-coated beads stimulate the formation of membrane extensions that ingest the beads into an early endosomal compartment. This LLO-induced internalization pathway is dynamin-and F-actin-dependent, and clathrin-independent. Interestingly, further linking pore formation to bacteria/bead uptake, LLO induces F-actin polymerization in a tyrosine kinase-and pore-dependent fashion. In conclusion, we demonstrate for the first time that a bacterial pathogen perforates the host cell plasma membrane as a strategy to activate the endocytic machinery and gain entry into the host cell

    Mathematical optimization in intensity modulated radiation therapy

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    The design of an intensity modulated radiotherapy treatment includes the selection of beam angles (geometry problem), the computation of an intensity map for each selected beam angle (intensity problem), and finding a sequence of configurations of a multileaf collimator to deliver the treatment (realization problem). Until the end of the last century research on radiotherapy treatment design has been published almost exclusively in the medical physics literature. However, since then, the attention of researchers in mathematical optimization has been drawn to the area and important progress has been made. In this paper we survey the use of optimization models, methods, and theories in intensity modulated radiotherapy treatment design

    Multifaceted Activity of Listeriolysin O, the Cholesterol-Dependent Cytolysin of Listeria monocytogenes

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    Mathematical optimization in intensity modulated radiation therapy

    No full text
    The design of an intensity modulated radiotherapy treatment includes the selection of beam angles (geometry problem), the computation of an intensity map for each selected beam angle (intensity problem), and finding a sequence of configurations of a multileaf collimator to deliver the treatment (realization problem). Until the end of the last century research on radiotherapy treatment design has been published almost exclusively in the medical physics literature. However, since then, the attention of researchers in mathematical optimization has been drawn to the area and important progress has been made. In this paper we survey the use of optimization models, methods, and theories in intensity modulated radiotherapy treatment design
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