Transkulturelle Erkundungen:wissenschaftliche-künstlerische Perspektiven

Dieses Werk präsentiert interdisziplinäre und internationale Zugänge zur Transkulturalität aus Philosophie, Politikwissenschaft, Ethnomusikologie, Popularmusikforschung, Gender und Queer-Studies, Musikwissenschaft, Musikpädagogik, Postcolonial Studies, Migrationsforschung und Minderheitenforschung. Es sind die nachhaltigen Ergebnisse einer Ringvorlesung an der Universität für Musik und darstellende Kunst Wien-mdw aus den Jahren 2014-2018, bei der Wissenschaft und Kunst in einen fruchtbaren Dialog traten

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma

PurposeThe purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).Experimental designRB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss.ResultsRB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1.ConclusionsCo-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation

Clustering schizophrenia genes by their temporal expression patterns aids functional interpretation

Background Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Study design We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls. Study results Clustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals. Conclusions We provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other’s effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia

Layered Fan-Planar Graph Drawings

In this paper, we study fan-planar drawings that use $h$ layers and are proper, i.e., edges connect adjacent layers. We show that if the embedding of the graph is fixed, then testing the existence of such drawings is fixed-parameter tractable in $h$, via a reduction to a similar result for planar graphs by Dujmovi\'{c} et al. If the embedding is not fixed, then we give partial results for $h=2$: It was already known how to test existence of fan-planar proper 2-layer drawings for 2-connected graphs, and we show here how to test this for trees. Along the way, we exhibit other interesting results for graphs with a fan-planar proper $h$-layer drawings; in particular we bound their pathwidth and show that they have a bar-1-visibility representation

Rights and wrongs of manager identity: Implications for manager development

In a rectilinear dual of a planar graph vertices are represented by simple rectilinear polygons and edges are represented by side-contact between the corresponding polygons. A rectilinear dual is called a cartogram if the area of each region is equal to a pre-specified weight of the corresponding vertex. The complexity of a cartogram is determined by the maximum number of corners (or sides) required for any polygon. In a series of papers the polygonal complexity of such representations for maximal planar graphs has been reduced from the initial 40 to 34, then to 12 and very recently to the currently best known 10. Here we describe a construction with 8-sided polygons, which is optimal in terms of polygonal complexity as 8-sided polygons are sometimes necessary. Specifically, we show how to compute the combinatorial structure and how to refine the representation into an area-universal rectangular layout in linear time. The exact cartogram can be computed from the area-universal rectangular layout with numerical iteration, or can be approximated with a hill-climbing heuristic. We also describe an alternative construction for Hamiltonian maximal planar graphs, which allows us to directly compute the cartograms in linear time. Moreover, we prove that even for Hamiltonian graphs 8-sided rectilinear polygons are necessary, by constructing a non-trivial lower bound example. The complexity of the cartograms can be reduced to 6 if the Hamiltonian path has the extra property that it is one-legged, as in outer-planar graphs. Thus, we have optimal representations (in terms of both polygonal complexity and running time) for Hamiltonian maximal planar and maximal outer-planar graphs.Comment: 18 pages, 7 figure