Neue Formen des Wettbewerbs um Fördermittel von EU, Bund und Ländern und die Wettbewerbsfähigkeit von Städten und Regionen

Europäische und nationale Fördermittel zur Verbesserung der regionalen Strukturen werden zunehmend im Rahmen von Wettbewerben vergeben. Bei dieser Form der Mittelvergabe treten oftmals Parameter wie „regionale Bedürftigkeit" oder geographische Besonderheiten in den Hintergrund, an denen sich früher die öffentlichen Förderstrategien ausgerichtet haben. Der Artikel beleuchtet die Ursachen, die zu der Änderung des Vergabeverfahrens geführt haben. Dabei wird deutlich, dass die Globalisierung und die zunehmende Innovationsförderung zur Erzielung von Produktivitätsfortschritten maßgeblich zu der neuen Vergabepraxis beigetragen haben. Wesentlichen Anteil an der Durchsetzung von Wettbewerbsverfahren hatten auch Behörden der EU, die zur Umsetzung ihrer Politik auf Partnerschaften mit regionalen und lokalen Akteuren angewiesen sind. In dem Artikel wird dargestellt, dass Wettbewerbe einen Beitrag liefern können, neuartige Pilotverfahren zu entwickeln und zusammen mit regionalen Partnern umzusetzen. Gleichzeitig kann diese Wettbewerbsorientierung zu einer Polarisierung zwischen Kommunen und Regionen führen und bestehende regionale Disparitäten verstärken.European and national subsidies intended to improve regional structures are increasingly being granted within a competitive framework. Parameters such as “regional need” or geographical specificities, which in the past were the focus of public subsidy strategies, often take a backseat with this form of subsidy award. This paper sheds light on the reasons that have led to the change in subsidy distribution. It becomes clear that globalisation and the increasing promotion of innovation intended to advance productivity have significantly contributed to the new award practices. An important role in the establishment of the competitive awards was also played by the EU authorities, who rely on partnerships with regional and local actors for the implementation of their policies. The article illustrates that competitions can contribute towards the development of new pilot processes and their implementation in cooperation with regional partners. At the same time this competitive orientation can lead to a polarisation between municipalities and regions and intensify existing regional disparities

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Patronage and social mobility in the aristocracies of the Principate

The dissertation is entitled "Patronage and social mobility in the aristocracies of the Principate". Patronage is defined as a reciprocal exchange relationship between men of unequal social status (municipal patronage is excluded). The work falls into three parts. In the first the language of patronage (patronus, cliens, amicus, beneficium, etc.) is defined; the reciprocity ethic implicit in the language is described; and the spheres of social life in which the patronal ideology was applied by Romans are located. The core of the dissertation is devoted to a description of the patronage networks extending from the emperor through the imperial aristocracy to the provincial aristocracy (in particular, that of North Africa). At each level a description is offered of the economic, social and political goods and services exchanged and the types of people who entered into the patron-client relationships. Further, there is an attempt to show that the fact that Rome remained a patronal society in the Principate has broad implications: the distribution of a variety of offices and honors depended solely on patronage; senators continued to be important patrons distributing their own as well as imperial beneficia to their clients; senators and equites were bound together in a single patronal network; and patronage is perhaps the best explanation for the increasing entry of provincials into the imperial aristocracy. Traditionally it has been argued that the importance of patronage in the Principate was diminished by increasingly rigid bureaucratic machinery in which appointments and promotions were based on merit and especially seniority. Chapter three provides a demonstration that the influence of these bureaucratic criteria on senatorial and equestrian careers have been greatly overestimated and that there is no reason to minimize the effects of patronage