Researching methods for efficient hardware specification, design and implementation of a next generation communication architecture

The objective of this work is to create and implement a System Area Network (SAN) architecture called EXTOLL embedded in the current world of systems, software and standards based on the experiences obtained during the ATOLL project development and test. The topics of this work also cover system design methodology and educational issues in order to provide appropriate human resources and work premises. The scope of this work in the EXTOLL SAN project was: • the Xbar architecture and routing (multi-layer routing, virtual channels and their arbitration, routing formats, dead lock aviodance, debug features, automation of reuse) • the on-chip module communication architecture and parts of the host communication • the network processor architecture and integration • the development of the design methodology and the creation of the design flow • the team education and work structure. In order to successfully leverage student know-how and work flow methodology for this research project the SEED curricula changes has been governed by the Hochschul Didaktik Zentrum resulting in a certificate for "Hochschuldidaktik" and excellence in university education. The complexity of the target system required new approaches in concurrent Hardware/Software codesign. The concept of virtual hardware prototypes has been established and excessively used during design space exploration and software interface design

Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1

Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults and plays a critical role in brain health and disease. We report that the core circadian clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism and a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation and inflammatory gene expression in vitro and in vivo, mediated in part by suppression of glutathione-S-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a mechanism by which the circadian clock could influence many aspects of brain function and neurological disease. [Display omitted] •Circadian disruption promotes astrocyte activation•Astrocyte-specific deletion of the circadian clock gene BMAL1 induces activation•BMAL1 regulates astrocyte activation by altering glutathione-S-transferase signaling•Loss of astrocyte BMAL1 enhances neuronal cell death in a co-culture system Lananna et al. show that the circadian clock protein BMAL1 regulates astrocyte activation via a cell-autonomous mechanism involving diminished glutathione-S-transferase signaling. This finding elucidates a function of the core circadian clock in astrocytes and reveals BMAL1 as a modulator of astrogliosis

Design of a cyclotide antagonist of neuropilin-1 and-2 that potently inhibits endothelial cell migration

Neuropilin-1 and -2 are critical regulators of angiogenesis, lymphangiogenesis, and cell survival as receptors for multiple growth factors. Disulfide-rich peptides that antagonize the growth factor receptors neuropilin-1 and neuropilin-2 were developed using bacterial display libraries. Peptide ligands specific for the VEGFA binding site on neuropilin-1 were identified by screening a library of disulfide-rich peptides derived from the thermostable, protease-resistant cyclotide kalata B1. First generation ligands were subjected to one cycle of affinity maturation to yield acyclic peptides with affinities of 40-60 nM and slow dissociation rate constants (similar to 1 X 10(-3) s(-1)). Peptides exhibited equivalent affinities for human and mouse neuropilin-1 and cross-reacted with human neuropilin-2 with lower affinity. A C-to-N cyclized variant (cyclotide) of one neuropilin ligand retained high affinity, exhibited increased protease resistance, and conferred improved potency for inhibiting endothelial cell migration in vitro (EC50 approximate to 00 nM). These results demonstrate that potent, target-specific cyclotides can be created by evolutionary design and that backbone cyclization can confer improved pharmacological properties