53 research outputs found

    A novel bacteriophage Tail-Associated Muralytic Enzyme (TAME) from Phage K and its development into a potent antistaphylococcal protein

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    <p>Abstract</p> <p>Background</p> <p><it>Staphylococcus aureus </it>is a major cause of nosocomial and community-acquired infections. However, the rapid emergence of antibiotic resistance limits the choice of therapeutic options for treating infections caused by this organism. Muralytic enzymes from bacteriophages have recently gained attention for their potential as antibacterial agents against antibiotic-resistant gram-positive organisms. Phage K is a polyvalent virulent phage of the <it>Myoviridae </it>family that is active against many <it>Staphylococcus </it>species.</p> <p>Results</p> <p>We identified a phage K gene, designated <it>orf</it>56, as encoding the phage tail-associated muralytic enzyme (TAME). The gene product (ORF56) contains a C-terminal domain corresponding to cysteine, histidine-dependent amidohydrolase/peptidase (CHAP), which demonstrated muralytic activity on a staphylococcal cell wall substrate and was lethal to <it>S. aureus </it>cells. We constructed N-terminal truncated forms of ORF56 and arrived at a 16-kDa protein (Lys16) that retained antistaphylococcal activity. We then generated a chimeric gene construct encoding Lys16 and a staphylococcal cell wall-binding SH3b domain. This chimeric protein (P128) showed potent antistaphylococcal activity on global clinical isolates of <it>S. aureus </it>including methicillin-resistant strains. In addition, P128 was effective in decolonizing rat nares of <it>S. aureus </it>USA300 in an experimental model.</p> <p>Conclusions</p> <p>We identified a phage K gene that encodes a protein associated with the phage tail structure. The muralytic activity of the phage K TAME was localized to the C-terminal CHAP domain. This potent antistaphylococcal TAME was combined with an efficient <it>Staphylococcus</it>-specific cell-wall targeting domain SH3b, resulting in the chimeric protein P128. This protein shows bactericidal activity against globally prevalent antibiotic resistant clinical isolates of <it>S. aureus </it>and against the genus <it>Staphylococcus </it>in general. <it>In vivo</it>, P128 was efficacious against methicillin-resistant <it>S. aureus </it>in a rat nasal colonization model.</p

    Response-time analysis and overload management in real-time systems

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    We provide two approaches to handling overload in shared resources offering realtime guarantees. We first provide a technique (based on mathematical optimization) for identifying the possible causes for an overload situation by computing the worst-case demand of the system, depending upon the amount of requests serviced. Worst-case analysis of response time has a pseudo-polynomial time complexity, and when there is no knowledge about the workload, the complexity further increases. We provide polynomial-time heuristics to reduce the computation time of the algorithm. Further, we evaluate it against other techniques using stochastic analysis to stress on the accuracy and ease of estimation of the result. The scheduling policy based on the approach is useful to detect an overload in the resource and to allow us to make responsible decisions on it. Secondly, we present a scheduling policy (obtained through stochastic approximation) to handle overload in real-time systems. Competitive analysis of online algorithms has commonly been applied to understand the behavior of real-time systems during overload conditions. While competitive analysis provides insight into the behavior of certain algorithms, it is hard to make inferences about the performance of those algorithms in practice. Similar on-line scheduling approaches tend to function differently in practice due to factors. Further, most work on handling overload in real-time systems does not consider using information regarding the distribution of arrival rates of jobs and execution times to make scheduling decisions. With some information about the workload, we aim to improve the revenue earned by the service provider, in a scenario when each successful job completion results in revenue accrual. We prove that the policy we outline does lead to increased revenue when compared to a class of scheduling policies that make static resource allocations to different service classes. We also use empirical evidence to underscore the fact that this policy performs better than a variety of other scheduling policies. The ideas presented can be applied to several soft real-time systems, specifically systems with multiple service classes.Applied Science, Faculty ofElectrical and Computer Engineering, Department ofGraduat

    *To appear in Journal of Object-Oriented Programming

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    study the use of information technology in both the private and public sectors and to enhance productivity in areas ranging from finance to transportation, and from manufacturing to telecommunications. &amp;quot; At the time of its inception, PROFIT took over the Composite Information Systems Laboratory and Handwritten Character Recognition Laboratory. These two laboratories are now involved in research related to context mediation and imaging respectively. In addition, PROFIT has undertaken joint efforts with a number of research centers, laboratories, and programs at MIT, and the results of these efforts are documented in Discussion Papers published by PROFIT and/or the collaborating MIT entity. Correspondence can be addressed to

    Incremental loading in the persistent C++ language E

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    "February 1994." "To appear in Journal of object-oriented programming."HD28 .M414 no.3774-, 95,

    Tuberous xanthoma with cardiac failure in a child

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    A 14-year-old girl presented with gradually progressive breathlessness for 3 weeks. On evaluation, it was found that she had left ventricular hypertrophy and nonprogressive R wave in ECG. An echocardiogram revealed aortic stenosis and severe left ventricular dysfunction.Computed Tomography (CT) imaging showed aortic annulus calcifications causing aortic stenosis. Over three years she had gradually developed asymptomatic cutaneous swellings over the small and large joints of the extremities suggestive of tuberous xanthomas. Skin biopsy revealed scattered foamy macrophages in the upper dermis and cholesterol clefts. Her lipid profile showed raised total cholesterol and low-density lipoprotein levels. With the above clinical, histological, and laboratory findings she was diagnosed as a case of familial homozygous hypercholesterolemia with tuberous xanthomas and cardiac failure. She was started on statins, ezetimibe, and other anti-failure measures. We present this case for its rarity. Early diagnosis of this condition based on skin findings, could have prevented cardiac failure by initiating early appropriate treatment
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