Necessary and Sufficient Conditions on Partial Orders for Modeling Concurrent Computations

Partial orders are used extensively for modeling and analyzing concurrent computations. In this paper, we define two properties of partially ordered sets: width-extensibility and interleaving-consistency, and show that a partial order can be a valid state based model: (1) of some synchronous concurrent computation iff it is width-extensible, and (2) of some asynchronous concurrent computation iff it is width-extensible and interleaving-consistent. We also show a duality between the event based and state based models of concurrent computations, and give algorithms to convert models between the two domains. When applied to the problem of checkpointing, our theory leads to a better understanding of some existing results and algorithms in the field. It also leads to efficient detection algorithms for predicates whose evaluation requires knowledge of states from all the processes in the system

SUCCESSFUL TREATMENT OF VENTILATOR ASSOCIATED PNEUMONIA CAUSED BY MULTIDRUG RESISTANT ACINETOBACTER BAUMANNII WITH A COMBINATION THERAPY OF CSE1034 AND COLISTIN: A CASE REPORT.

 Objective: One of the major causes of ventilator-associated pneumonia (VAP) in hospital settings is Acinetobacter baumannii. The propensity of acquiring antimicrobial resistance rapidly through a multiple number of mechanisms makes the selection of an appropriate empirical antimicrobial agent exceedingly challenging for this pathogen.Methods: The present case report explores the option of treating VAP infection due to carbapenem-resistant pathogens with antibiotic adjuvant entities.Results: We present a case of VAP due to carbapenem-resistant A. baumannii that was successfully treated with CSE-1034 and colistin combination therapy.Conclusion: Early recognition and appropriate antibiotic therapy are essential to eliminate poor outcomes in multidrug-resistant (MDR) bacterial infections. The present case highlights the antibiotic adjuvant entity CSE-1034†as an empiric option for the treatment of VAP due to MDR A. baumannii in intensive care unit

ActiveMonitor: Asynchronous Monitor Framework for Scalability and Multi-Object Synchronization

Monitor objects are used extensively for thread-safety and synchronization in shared memory parallel programs. They provide ease of use, and enable straightforward correctness analysis. However, they inhibit parallelism by enforcing serial executions of critical sections, and thus the performance of parallel programs with monitors scales poorly with number of processes. Their current design and implementation is also ill-suited for thread synchronization across multiple thread-safe objects. We present ActiveMonitor - a framework that allows multi-object synchronization without global locks, and improves parallelism by exploiting asynchronous execution of critical sections. We evaluate the performance of Java based implementation of ActiveMonitor on micro-benchmarks involving light and heavy critical sections, as well as on single-source-shortest-path problem in directed graphs. Our results show that on most of these problems, ActiveMonitor based programs outperform programs implemented using Java\u27s reentrant-lock and condition constructs

Photo-activation of the hydrophobic probe iodonaphthylazide in cells alters membrane protein function leading to cell death

<p>Abstract</p> <p>Background</p> <p>Photo-activation of the hydrophobic membrane probe 1, 5 iodonaphthylazide (INA) by irradiation with UV light (310–380 nm) results in the covalent modification of transmembrane anchors of membrane proteins. This unique selectivity of INA towards the transmembrane anchor has been exploited to specifically label proteins inserted in membranes. Previously, we have demonstrated that photo-activation of INA in enveloped viruses resulted in the inhibition of viral membrane protein-induced membrane fusion and viral entry into cells. In this study we show that photo-activation of INA in various cell lines, including those over-expressing the multi-drug resistance transporters MRP1 or Pgp, leads to cell death. We analyzed mechanisms of cell killing by INA-UV treatment. The effects of INA-UV treatment on signaling via various cell surface receptors, on the activity of the multi-drug resistance transporter MRP1 and on membrane protein lateral mobility were also investigated.</p> <p>Results</p> <p>INA treatment of various cell lines followed by irradiation with UV light (310–380 nm) resulted in loss of cell viability in a dose dependent manner. The mechanism of cell death appeared to be apoptosis as indicated by phosphatidylserine exposure, mitochondrial depolarization and DNA fragmentation. Inhibition by pan-caspase inhibitors and cleavage of caspase specific substrates indicated that at low concentrations of INA apoptosis was caspase dependent. The INA-UV treatment showed similar cell killing efficacy in cells over-expressing MRP1 function as control cells. Efflux of an MRP1 substrate was blocked by INA-UV treatment of the MRP1-overexpressing cells. Although INA-UV treatment resulted in inhibition of calcium mobilization triggered by chemokine receptor signaling, Akt phosphorylation triggered by IGF1 receptor signaling was enhanced. Furthermore, fluorescence recovery after photobleaching experiments indicated that INA-UV treatment resulted in reduced lateral mobility of a seven transmembrane G protein-coupled receptor.</p> <p>Conclusion</p> <p>INA is a photo-activable agent that induces apoptosis in various cancer cell lines. It reacts with membrane proteins to alter the normal physiological function resulting in apoptosis. This activity of INA maybe exploited for use as an anti-cancer agent.</p

Different thresholds of T cell activation regulate FIV infection of CD4+CD25+ and CD4+CD25− cells

AbstractCellular activation plays an important role in retroviral replication. Previously, we have shown that CD4+CD25+ T cells by the virtue of their partially activated phenotype represent ideal candidates for a productive feline immunodeficiency virus (FIV) infection. In the present study, we extended our previous observations with regard to FIV replication in CD4+CD25+ and CD4+CD25− cells under different stimulation conditions. Both CD4+CD25+ and CD4+CD25− cells remain latently infected in the absence of IL-2 or concanvalinA (ConA), respectively; harboring a replication competent provirus capable of reactivation several days post-infection. While CD4+CD25+ cells require low levels of exogenous IL-2 and virus inputs for an efficient FIV replication, CD4+CD25− T cells can only be productively infected in the presence of either high concentrations of IL-2 or high virus titers, even in the absence of mitogenic stimulation. Interestingly, while high virus input activates CD4+CD25− cells to replicate FIV, it induces apoptosis in a high percentage of CD4+CD25+ T cells. High IL-2 concentrations but not high virus inputs lead to surface upregulation of CD25 and significant cellular proliferation in CD4+CD25− cells. These results suggest that CD4+CD25+ and CD4+CD25− T cells have different activation requirements which can be modulated by both viral and cytokine stimuli to reach threshold activation levels in order to harbor a productive FIV infection. This holds implications in vivo for CD4+CD25+ and CD4+CD25− cells to serve as potential reservoirs of a productive and latent FIV infection