An den Rändern

Der Katalog erscheint anlässlich der Ausstellung von Michael Cleffs Arbeiten im Herbst 2017 im Kunstmuseum Ahlen. Es werden die drei Werkgruppen Plastik, Zeichnung und Fotografie vorgestellt. Die Ausstellung und alle Arbeiten hat der Essener Fotograf Christian Schlüter dokumentiert. Zu Cleffs Plastiken und Installationen hat Roland Mönig, Leiter des Saarlandmuseums in Saarbrücken, eine Einführung unter dem Titel Ausweitung der Randzone verfasst. Das zeichnerische Werk wurde von der Kunsthistorikerin und Künstlerin Sandra del Pilar in dem Kapitel Michael Cleff: Zeit der Materie besprochen. Die Künstlerin und Hochschullehrerin Barbara Christin setzt sich mit den fotografischen Arbeiten auseinander: Im Material – Fotografien von Michael Cleff. Die Übersetzung ins Englische besorgte John Brogden. Dieser Katalog erscheint anlässlich der Ausstellung:This catalogue is published in conjunction with the exhibition: Michael CleffAn den Rändern.On Margins. Kunstmuseum Ahlen/Westfalen6. August – 1. Oktober 2017 www.kunstmuseum-ahlen.d

Bisulfite profiling of the MGMT promoter and comparison with routine testing in glioblastoma diagnostics

Background: Promoter methylation of the DNA repair gene O6 -methylguanine-DNA methyltransferase (MGMT) is an acknowledged predictive epigenetic marker in glioblastoma multiforme and anaplastic astrocytoma. Patients with methylated CpGs in the MGMT promoter beneft from treatment with alkylating agents, such as temozolomide, and show an improved overall survival and progression-free interval. A precise determination of MGMT promoter methyla‑ tion is of importance for diagnostic decisions. We experienced that diferent methods show partially divergent results in a daily routine. For an integrated neuropathological diagnosis of malignant gliomas, we therefore currently apply a combination of methylation-specifc PCR assays and pyrosequencing. Results: To better rationalize the variation across assays, we compared these standard techniques and assays to deep bisulfte sequencing results in a cohort of 80 malignant astrocytomas. Our deep analysis covers 49 CpG sites of the expanded MGMT promoter, including exon 1, parts of intron 1 and a region upstream of the transcription start site (TSS). We observed that deep sequencing data are in general in agreement with CpG-specifc pyrosequencing, while the most widely used MSP assays published by Esteller et al. (N Engl J Med 343(19):1350–1354, 2000. https://doi.org/ 10.1056/NEJM200011093431901) and Felsberg et al. (Clin Cancer Res 15(21):6683–6693, 2009. https://doi.org/10.1158/ 1078-0432.CCR-08-2801) resulted in partially discordant results in 22 tumors (27.5%). Local deep bisulfte sequencing (LDBS) revealed that CpGs located in exon 1 are suited best to discriminate methylated from unmethylated samples. Based on LDBS data, we propose an optimized MSP primer pair with 83% and 85% concordance to pyrosequencing and LDBS data. A hitherto neglected region upstream of the TSS, with an overall higher methylation compared to exon 1 and intron 1 of MGMT, is also able to discriminate the methylation status. Conclusion: Our integrated analysis allows to evaluate and redefne co-methylation domains within the MGMT pro‑ moter and to rationalize the practical impact on assays used in daily routine diagnostics

Living Labs für nachhaltige Entwicklung : Potenziale einer Forschungsinfrastruktur zur Nutzerintegration in der Entwicklung von Produkten und Dienstleistungen

Die Studie untersucht das Potential der deutschen Forschungslandschaft für nutzerintegrierende Produkt- und Dienstleistungsinnovationen. Sie zeigt auf, dass Living Labs mit zunehmender Mensch-Technik-Interaktion eine wichtige Rolle für nachhaltige Entwicklung spielen können. Living Labs zielen auf eine frühzeitige Integration von Nutzerbedürfnissen und des Anwendungskontextes in Forschungs- und Innovationsprozesse. Sie können beispielsweise Lösungen zur Erhöhung der Akzeptanz ressourcenschonender Systemlösungen oder zur Vermeidung von negativen systemischen Auswirkungen auf den Ressourcen- und Energieverbrauch bieten. In der Potentialstudie werden Anwendungsfelder von Living Labs identifiziert sowie Aspekte, die für die Entwicklung des Forschungs- und Innovationssystems relevant sind, untersucht. Weiterhin werden Handlungsoptionen zur Förderung transdisziplinärer Verbundprojekte und zu strukturbildenden Maßnahmen aufgezeigt. Die Studie basiert auf den Ergebnissen des Projekts "Nachhaltigkeitsinnovationen im Living Lab", welches vom Bundesministerium für Bildung und Forschung (BMBF) gefördert wurde, und ist am Wuppertal Institut in Zusammenarbeit mit dem Fraunhofer-Institut für Arbeitswirtschaft und Organisation (IAO), dem Fraunhofer-Institut für System- und Innovationsforschung (ISI) sowie dem Faktor 10-Institut entstanden ist

Bisulfite profiling of the MGMT promoter and comparison with routine testing in glioblastoma diagnostics

Background: Promoter methylation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is an acknowledged predictive epigenetic marker in glioblastoma multiforme and anaplastic astrocytoma. Patients with methylated CpGs in the MGMT promoter benefit from treatment with alkylating agents, such as temozolomide, and show an improved overall survival and progression-free interval. A precise determination of MGMT promoter methylation is of importance for diagnostic decisions. We experienced that different methods show partially divergent results in a daily routine. For an integrated neuropathological diagnosis of malignant gliomas, we therefore currently apply a combination of methylation-specific PCR assays and pyrosequencing. Results: To better rationalize the variation across assays, we compared these standard techniques and assays to deep bisulfite sequencing results in a cohort of 80 malignant astrocytomas. Our deep analysis covers 49 CpG sites of the expanded MGMT promoter, including exon 1, parts of intron 1 and a region upstream of the transcription start site (TSS). We observed that deep sequencing data are in general in agreement with CpG-specific pyrosequencing, while the most widely used MSP assays published by Esteller et al. (N Engl J Med 343(19):1350-1354, 2000. https://doi.org/10.1056/NEJM200011093431901 ) and Felsberg et al. (Clin Cancer Res 15(21):6683-6693, 2009. https://doi.org/10.1158/1078-0432.CCR-08-2801 ) resulted in partially discordant results in 22 tumors (27.5%). Local deep bisulfite sequencing (LDBS) revealed that CpGs located in exon 1 are suited best to discriminate methylated from unmethylated samples. Based on LDBS data, we propose an optimized MSP primer pair with 83% and 85% concordance to pyrosequencing and LDBS data. A hitherto neglected region upstream of the TSS, with an overall higher methylation compared to exon 1 and intron 1 of MGMT, is also able to discriminate the methylation status. Conclusion: Our integrated analysis allows to evaluate and redefine co-methylation domains within the MGMT promoter and to rationalize the practical impact on assays used in daily routine diagnostics.Funding: Open Access funding enabled and organized by Projekt DEAL. This work was supported by the German Epigenome Programme (DEEP) of the Federal Ministry of Education and Research in Germany (BMBF) (01KU1216F). MS is supported by the BMBF project de.NBI-epi (031L0101D) and the EU H2020 project SYSCID (733100

Results from a 1-year, open-label, single arm, multi-center trial evaluating the efficacy and safety of oral Deferasirox in patients diagnosed with low and int-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent iron overload

The majority of patients with myelodysplastic syndrome (MDS) present with anemia and will become dependent on regular transfusions of packed red blood cells (PRBC) with the risk of iron overload (IOL). Liver iron content best reflects the total body iron content, and measurement of liver iron concentration (LIC) by MRI is a validated tool for detection, but data in MDS is rather limited. Here we present the results of a multi-center trial evaluating the efficacy and safety of deferasirox (DFX) in low and intermediate-1 risk MDS patients with transfusion-dependent IOL. Three patients with transfusion frequency of > 4 units PRBC per month were initially treated with 30 mg/kg/day while in 46 patients with a lower transfusion burden deferasirox was initiated at 20 mg/kg/day, due to patient related reasons one patient received DFX in a dose of 6 mg/kg/day only. LIC was measured by MRI at baseline and end of study using the method by St. Pierre et al. The intention to treat population consisted of 50 MDS patients (28 male; 22 female) with a median age of 69 years who were treated with DFX for a median duration of 354 days. Mean daily dose of DFX was 19 mg/kg/day. Median serum ferritin level (SF) at baseline was 2,447 ng/mL and decreased to 1,685 ng/mL (reduction by 31 %) at end of study (p = 0.01). In 7 (13 %) patients the initially chosen dose had to be increased due to unsatisfactory efficacy of chelation therapy. For 21 patients, LIC measurement by liver MRI was performed at baseline and for 19 of these patients at the end of study: mean LIC decreased significantly from 16,8 mg/g dry tissue weight (+/- 8.3 mg/g dry tissue weight) at study entry to 10,8 mg/g dry tissue weight (+/- 10.4 mg/g dry tissue weight) at end of study (p = 0.01). Of all patients exposed to the study drug (n = 54), 28 (52 %) did not complete the 12 month study period most commonly due to AEs in 28 % (n = 15) and abnormal laboratory values in 7 % (n = 4), respectively. The most common adverse events (a parts per thousand yenaEuro parts per thousand 10 % of all patients) with suspected drug relationship were diarrhea (n = 25, 46 %), nausea (n = 13, 24 %), upper abdominal pain (n = 8, 15 %), serum creatinine increase (n = 16, 30 %) and rash (n = 5, 9 %). Adverse events making dose adjustments or interruption of study drug necessary occurred in 33 patients (61 %). Hematologic improvement according to IWG criteria (2006) was observed in 6 patients (11 %). Initiation of treatment of IOL with DFX depending on the transfusion burden yields sufficient reduction of excess iron indicated by serum ferritin levels and most importantly by liver MRI. The safety profile of DFX was comparable to previous observations

RADICAL IONS AND PHOTOCHEMICAL CHARGE-TRANSFER PHENOMENA .16. PHOTOREACTIONS OF BIACETYL WITH ELECTRON-RICH OLEFINS - AN EXTENDED MECHANISM

Mattay J, GERSDORF J, BUCHKREMER K. RADICAL IONS AND PHOTOCHEMICAL CHARGE-TRANSFER PHENOMENA .16. PHOTOREACTIONS OF BIACETYL WITH ELECTRON-RICH OLEFINS - AN EXTENDED MECHANISM. Chemische Berichte. 1987;120(3):307-318