No abstract

The mechanisms involving iron toxicity in diabetes mellitus are not completely understood. However, the spontaneous reaction of reducing sugars with protein amino groups, known as glycation, has been shown to compromise the action of Tf (transferrin), the systemic iron transporter. In order to understand the structural alterations that impair its function, Tf was glycated in vitro and the modification sites were determined by MS. Iron binding to glycated Tf was assessed and a computational approach was conducted to study how glycation influences the iron-binding capacity of this protein. Glycated Tf samples were found to bind iron less avidly than non-modified Tf and MS results revealed 12 glycation sites, allowing the establishment of Lys534 and Lys206 as the most vulnerable residues to this modification. Their increased susceptibility to glycation was found to relate to their low side-chain pKa values. Lys534 and Lys206 participate in hydrogen bonding crucial for iron stabilization in the C- and N-lobes of the protein respectively, and their modification is bound to influence iron binding. Furthermore, the orientation of the glucose residues at these sites blocks the entrance to the iron-binding pocket. Molecular dynamics simulations also suggested that additional loss of iron binding capacity may result from the stereochemical effects induced by the glycation of lysine residues that prevent the conformational changes (from open to closed Tf forms) required for metal binding. Altogether, the results indicate that Tf is particularly vulnerable to glycation and that this modification targets spots that are particularly relevant to its function.

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The mainline Linux Kernel is not designed for hard real-time systems; it only fits the requirements of soft real-time systems. In recent years, a kernel developer community has been working on the PREEMPT-RT patch. This patch (that aims to get a fully preemptible kernel) adds some real-time capabilities to the Linux kernel. However, in terms of scheduling policies, the real-time scheduling class of Linux is limited to the First-In-First-Out (SCHED_FIFO) and Round-Robin (SCHED_RR) scheduling policies. These scheduling policies are however quite limited in terms of real-time performance. Therefore, in this paper, we report one important contribution for adding more advanced real-time capabilities to the Linux Kernel. Specifically, we describe modifications to the (PREEMPT-RT patched) Linux kernel to support real-time slot-based task-splitting scheduling algorithms. Our preliminary evaluation shows that our implementation exhibits a real-time performance that is superior to the scheduling policies provided by the current version of PREMPT-RT. This is a significant add-on to a widely adopted operating system.

Abstract. Several trends in society in general, and manufacturing in particular, have changed the way business was made in the last decades of the 20th century, setting new requirements for companies and individuals. The research question being addressed in this paper is concerned with the ability to build computer-supported manufacturing systems able to cope with current and future requirements. For this matter, a hypothesis based on the holonic and multi-agent paradigms is proposed. The paper describes a holonic architecture for manufacturing enterprises and a prototype system (named Fabricare) for manufacturing orders scheduling based on that architecture.A negotiation mechanism called 'contract net with constraint propagation protocol' was developed for regulating the interaction between holons in the system. This protocol also implements a negotiation-driven scheduling procedure.