Innovation business plan at Siemens: Portfolio-based roadmapping to focus on promising innovation projects right from the beginning

Roadmapping is an effective tool for supporting innovation projects and business strategies. It is easy to implement and can be used in many different ways. In an international and globally operating company like Siemens, roadmapping offers senior management a valuable aid for decision-making that is easy to understand in any language. Siemens has developed a supportive approach to decision-making known as the innovation business plan. The core of this innovation business plan consists of a portfolio-based roadmapping process. The purpose of this paper is to provide an overview of the above-mentioned portfolio-based roadmapping approach within the innovation business plan and its compilation in the organization

The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions

Acute and chronic inflammatory disorders are characterized by detrimental cytokine and chemokine expression. Frequently, the chemotactic activity of cytokines depends on a modified N-terminus of the polypeptide. Among those, the N-terminus of monocyte chemoattractant protein 1 (CCL2 and MCP-1) is modified to a pyroglutamate (pE-) residue protecting against degradation in vivo. Here, we show that the N-terminal pE-formation depends on glutaminyl cyclase activity. The pE-residue increases stability against N-terminal degradation by aminopeptidases and improves receptor activation and signal transduction in vitro. Genetic ablation of the glutaminyl cyclase iso-enzymes QC (QPCT) or isoQC (QPCTL) revealed a major role of isoQC for pE(1)-CCL2 formation and monocyte infiltration. Consistently, administration of QC-inhibitors in inflammatory models, such as thioglycollate-induced peritonitis reduced monocyte infiltration. The pharmacologic efficacy of QC/isoQC-inhibition was assessed in accelerated atherosclerosis in ApoE3*Leiden mice, showing attenuated atherosclerotic pathology following chronic oral treatment. Current strategies targeting CCL2 are mainly based on antibodies or spiegelmers. The application of small, orally available inhibitors of glutaminyl cyclases represents an alternative therapeutic strategy to treat CCL2-driven disorders such as atherosclerosis/restenosis and fibrosis