Perturbation of the stability of amyloid fibrils through alteration of electrostatic interactions.

The self-assembly of proteins and peptides into polymeric amyloid fibrils is a process that has important implications ranging from the understanding of protein misfolding disorders to the discovery of novel nanobiomaterials. In this study, we probe the stability of fibrils prepared at pH 2.0 and composed of the protein insulin by manipulating electrostatic interactions within the fibril architecture. We demonstrate that strong electrostatic repulsion is sufficient to disrupt the hydrogen-bonded, cross-β network that links insulin molecules and ultimately results in fibril dissociation. The extent of this dissociation correlates well with predictions for colloidal models considering the net global charge of the polypeptide chain, although the kinetics of the process is regulated by the charge state of a single amino acid. We found the fibrils to be maximally stable under their formation conditions. Partial disruption of the cross-β network under conditions where the fibrils remain intact leads to a reduction in their stability. Together, these results support the contention that a major determinant of amyloid stability stems from the interactions in the structured core, and show how the control of electrostatic interactions can be used to characterize the factors that modulate fibril stability.

Free-space optoelectronic switching cores with MPLS for SANs over WDM ring networks

With increasing demands on storage devices in the modern communication environment, the storage area network (SAN) has evolved to provide a direct connection allowing these storage devices to be accessed efficiently. To optimize the performance of a SAN, a three-stage hybrid electronic/optical switching node architecture based on the concept of a MPLS label switching mechanism, aimed at serving as a multi-protocol label switching (MPLS) ingress label edge router (LER) for a SAN-enabled application, has been designed. New shutter-based free-space multi-channel optical switching cores are employed as the core switch fabric to solve the packet contention and switching path conflict problems. The system-level node architecture design constraints are evaluated through self-similar traffic sourced from real gigabit Ethernet network traces and storage systems. The extension performance of a SAN over a proposed WDM ring network, aimed at serving as an MPLS-enabled transport network, is also presented and demonstrated. © 2012 OSA.

Change propagation analysis in complex technical systems

Understanding how and why changes propagate during engineering design is critical because most products and systems emerge from predecessors and not through clean sheet design. This paper applies change propagation analysis methods and extends prior reasoning through examination of a large data set from industry including 41,500 change requests, spanning 8 years during the design of a complex sensor system. Different methods are used to analyze the data and the results are compared to each other and evaluated in the context of previous findings. In particular the networks of connected parent, child and sibling changes are resolved over time and mapped to 46 subsystem areas. A normalized change propagation index (CPI) is then developed, showing the relative strength of each area on the absorber-multiplier spectrum between -1 and +1. Multipliers send out more changes than they receive and are good candidates for more focused change management. Another interesting finding is the quantitative confirmation of the "ripple" change pattern. Unlike the earlier prediction, however, it was found that the peak of cyclical change activity occurred late in the program driven by systems integration and functional testing. Patterns emerged from the data and offer clear implications for technical change management approaches in system design. Copyright © 2007 by ASME.