The C-terminus of Raf-1 acts as a 14-3-3-dependent activation switch

The Raf-1 protein kinase is a major activator of the ERK MAPK pathway, which links signaling by a variety of cell surface receptors to the regulation of cell proliferation, survival, differentiation and migration. Signaling by Raf-1 is regulated by a complex and poorly understood interplay between phosphorylation events and protein-protein interactions. One important mode of Raf-1 regulation involves the phosphorylation-dependent binding of 14-3-3 proteins. Here, we have examined the mechanism whereby the C-terminal 14-3-3 binding site of Raf-1, S621, controls the activation of MEK-ERK signaling. We show that phosphorylation of S621 turns over rapidly and is enriched in the activated pool of endogenous Raf-1. The phosphorylation on this site can be mediated by Raf-1 itself but also by other kinase(s). Mutations that prevent the binding of 14-3-3 proteins to S621 render Raf-1 inactive by specifically disrupting its capacity to bind to ATP, and not by gross conformational alteration as indicated by intact MEK binding. Phosphorylation of S621 correlates with the inhibition of Raf-1 catalytic activity in vitro, but 14-3-3 proteins can completely reverse this inhibition. Our findings suggest that 14-3-3 proteins function as critical cofactors in Raf-1 activation, which induce and maintain the protein in a state that is competent for both ATP binding and MEK phosphorylation.

Asymmetrical switch costs in children

Switching between tasks produces decreases in performance as compared to repeating the same task. Asymmetrical switch costs occur when switching between two tasks of unequal difficulty. This asymmetry occurs because the cost is greater when switching to the less difficult task than when switching to the more difficult task. Various theories about the origins of these asymmetrical switch costs have emerged from numerous and detailed experiments with adults. There is no documented evidence of asymmetrical switch costs in children. We conducted a series of studies that examined age-related changes in asymmetrical switch costs, within the same paradigm. Similarities in the patterns of asymmetrical switch costs between children and adults suggested that theoretical explanations of the cognitive mechanisms driving asymmetrical switch costs in adults could be applied to children. Age-related differences indicate that these theoretical explanations need to incorporate the relative contributions and interactions of developmental processes and task mastery. © 2006 Elsevier Inc. All rights reserved.

Optical grooming switch with regenerative functionality for transparent interconnection of networks

We demonstrate a regenerative optical grooming switch for buffer-less interconnection of metro/access and metro/core ring networks with switching functionality in time, space and wavelength domain. Key functionalities of the router are the traffic aggregation with time-slot interchanging (TSI) functionality, the WDM-to-ODTM multiplexing and the OTDM-to-WDM demultiplexing of high-speed channel into lower bit-rate tributaries as well as multi-wavelength all-optical 2R regeneration of several higher-speed signals. BER and Q-factor measurements of different switching scenarios show excellent performance with no error floor and Q-factors above 21 dB.

An all-optical grooming switch for interconnecting access and metro ring networks

A regenerative all-optical grooming switch for interconnecting 130 Gbit/s on-off keying (OOK) metro/core ring and 43 Gbit/s-OOK metro/access ring networks with switching functionality in time, space, and wavelength domains is demonstrated. Key functionalities of the switch are traffic aggregation with time-slot interchanging functionality, optical time division multiplexing (OTDM) to wavelength division multiplexing (WDM) demultiplexing, and multi-wavelength 2R regeneration. Laboratory and field demonstrations show the excellent performance of the new concept with error-free signal transmission and Q-factors above 20 dB.

Field experiments with a grooming switch for OTDM meshed networking

Field experiments of 42.7/128.1 Gb/s wavelength-division multiplexed, optical time-division multiplexed (WDM-OTDM) transmultiplexing and all-optical dual-wavelength regeneration at the OTDM rate are presented in this paper. By using the asynchronous retiming scheme, we achieve error-free bufferless data grooming with time-slot interchange capability for OTDM meshed networking. We demonstrate excellent performance from the system, discuss scalability, applicability, and the potential reach of the asynchronous retiming scheme for transparent OTDM-domain interconnection.