GPVI and GPIbα Mediate Staphylococcal Superantigen-Like Protein 5 (SSL5) Induced Platelet Activation and Direct toward Glycans as Potential Inhibitors

Background Staphylococcus aureus (S. aureus) is a common pathogen capable of causing life-threatening infections. Staphylococcal superantigen-like protein 5 (SSL5) has recently been shown to bind to platelet glycoproteins and induce platelet activation. This study investigates further the interaction between SSL5 and platelet glycoproteins. Moreover, using a glycan discovery approach, we aim to identify potential glycans to therapeutically target this interaction and prevent SSL5-induced effects. Methodology/Principal Findings In addition to platelet activation experiments, flow cytometry, immunoprecipitation, surface plasmon resonance and a glycan binding array, were used to identify specific SSL5 binding regions and mediators. We independently confirm SSL5 to interact with platelets via GPIbα and identify the sulphated-tyrosine residues as an important region for SSL5 binding. We also identify the novel direct interaction between SSL5 and the platelet collagen receptor GPVI. Together, these receptors offer one mechanistic explanation for the unique functional influences SSL5 exerts on platelets. A role for specific families of platelet glycans in mediating SSL5-platelet interactions was also discovered and used to identify and demonstrate effectiveness of potential glycan based inhibitors in vitro. Conclusions/Significance These findings further elucidate the functional interactions between SSL5 and platelets, including the novel finding of a role for the GPVI receptor. We demonstrate efficacy of possible glycan-based approaches to inhibit the SSL5-induced platelet activation. Our data warrant further work to prove SSL5-platelet effects in viv

Analysis of Balanced Fork-Join Queueing Networks

This paper presents an analysis of closed, balanced, fork-join queueing networks with exponential service time distributions. The fork-join queue is mapped onto two non-parallel networks, namely, a serial-join model and a state-dependent model. Using these models, it is proven that the proportion of the number of jobs in the different subsystems of the fork-join queueing network remains constant, irrespective of the multiprogramming level. This property of balanced fork-join networks is used to compute quick, inexpensive bounds for arbitrary fork-join networks

The Performance of Non-Redundant Striping in a SSA Disk Array

An increasingly popular method of improving I/O performance is by distributing data across multiple disks in parallel. This organization of data is called striping, and a group of disks organized in this manner is called a disk array. This work investigates the performance of striping data in an array of Serial Storage Architecture (SSA) disks connected in a loop topology