Matthias Hoffmann

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BACKGROUND The mitotic kinases, Cdk1, Aurora A/B, and Polo-like kinase 1 (Plk1) have been characterized extensively to further understanding of mitotic mechanisms and as potential targets for cancer therapy. Cdk1 and Aurora kinase studies have been facilitated by small-molecule inhibitors, but few if any potent Plk1 inhibitors have been identified. (More)
Hormones and growth factors induce the activation of a number of protein kinases that belong to the AGC subfamily, including isoforms of PKA, protein kinase B (also known as Akt), PKC, S6K p70 (ribosomal S6 kinase), RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated protein kinase), which then mediate many of the physiological processes(More)
Fine-mapping of the cell-division cycle, notably the identification of mitotic kinase signaling pathways, provides novel opportunities for cancer-drug discovery. As a key regulator of multiple steps during mitotic progression across eukaryotic species, the serine/threonine-specific Polo-like kinase 1 (Plk1) is highly expressed in malignant cells and serves(More)
Tools for managing systems requirements help keeping specifications consistent, up-to-date and accessible. Since the requirements for complex systems are themselves complex information structures that must be handled in complex process scenarios, there are many strong requirements concerning a tool for managing them. This paper presents a requirements(More)
PURPOSE Antimitotic chemotherapy remains a cornerstone of multimodality treatment for locally advanced and metastatic cancers. To identify novel mitosis-specific agents with higher selectivity than approved tubulin-binding agents (taxanes, Vinca alkaloids), we have generated inhibitors of Polo-like kinase 1, a target that functions predominantly in mitosis.(More)
High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model(More)
N-terminal pyroglutamate (pGlu) formation from glutaminyl precursors is a posttranslational event in the processing of bioactive neuropeptides such as thyrotropin-releasing hormone and neurotensin during their maturation in the secretory pathway. The reaction is facilitated by glutaminyl cyclase (QC), an enzyme highly abundant in mammalian brain. Here, we(More)
OBJECTIVES To limit exposure to anti-HIV drugs and minimize risk of long-term side effects, studies have looked at the possibility of simplified maintenance strategies. Ritonavir-boosted protease-inhibitor (PI)-monotherapies are an attractive alternative, but limited compartmental penetration of PI remains a concern. DESIGN Non-comparative 24-week pilot(More)
Electroanatomical Mapping (CARTO®) allows a tridimensional localization of ectopic atrial tachycardia (EAT). No standardized recommendation exists for annotation the local activation time in EAT using this new technology. In the present study bipolar local electrogram were used for CARTO® guided RF ablation of EAT. In comparison the same maps were(More)
Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly growing NTM, however, are lacking. We present here one case of PVE and one case of bloodstream infection caused by Mycobacterium chimaera. Randomly amplified polymorphic DNA (RAPD)-PCR indicated a relatedness of(More)