Glioblastoma remains one of the most challenging forms of cancer to treat. Here, we develop a computational platform that integrates the analysis of copy number variations and somatic mutations and unravels the landscape of in-frame gene fusions in glioblastoma. We find mutations with loss of heterozygosity of LZTR-1, an adaptor of Cul3-containing E3 ligase complexes. Mutations and deletions disrupt LZTR-1 function, which restrains self-renewal and growth of glioma spheres retaining stem cell features. Loss-of-function mutations of CTNND2 target a neural-specific gene and are associated with transformation of glioma cells along the very aggressive mesenchymal phenotype. We also report recurrent translocations that fuse the coding sequence of EGFR to several partners, with EGFR-SEPT14 as the most frequent functional gene fusion in human glioblastoma. EGFR-SEPT14 fusions activate Stat3 signaling and confer mitogen independency and sensitivity to EGFR inhibition. These results provide important insights into the pathogenesis of glioblastoma and highlight new targets for therapeutic intervention.

A series of well-defined poly(3-hexylthiophene)s (P3HT) of different molecular weight (MW) and high regioregularity was investigated for charge transport properties in ascast and melt-crystallized films. The semicrystalline structure of the P3HT was characterized by X-ray scattering and Atomic force microscopy. Crystallization by cooling from the melt led to a substantial increase in crystallinity and a stronger alignment of the crystals in comparison to as-cast films. The increase in crystallinity went along with an increase in hole mobility of up to an order of magnitude as measured by the space charge limited current method. Additionally, the hole mobility depended on the long period of P3HT lamellae and consequently on the MW. In compliance with the long period, the charge carrier mobility first increased with the MW before decreasing again at the onset of chain folding. V C 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 943-951

Microphase-separated donor–acceptor block copolymers have been discussed as ideal systems for morphology control in organic photovoltaics. Typical microphases as known from coil–coil systems were not observed in such systems due to crystallization dominating over microphase separation. We show how this problem can be overcome by the synthesis of high molecular weight block copolymers leading to a high enough χN parameter and microphase separation in the melt. A combination of copper-catalyzed azide-alkyne click reaction and nitroxide mediated radical polymerization (NMRP) was used for the synthesis of donor–acceptor poly(3-hexylthiophene)-block-poly perylene bisimide acrylate (P3HT-b-PPerAcr) block copolymers. With this synthetic strategy, high molecular weights are possible and no triblock copolymer byproducts are formed, as observed with former methods. Two different block copolymers with a high molecular weight P3HT block of 19.7 kg/mol and a PPerAcr content of 47 and 64 wt % were obtained. X-ray scattering measurements show that the diblock copolymers exhibit microphase separation in the melt state. Furthermore, upon cooling confined crystallization occurs inside the microphase separated domains without destroying the microphase order. The observed microstructures fit well to the respective volume fractions and the crystalline packing within the individual blocks is analogous to those in the respective homopolymers. For the first time, typical lamellar or cylindrical phase separated structures as known for amorphous coil–coil systems are realized for a crystalline–liquid crystalline, donor–acceptor block copolymer. A similar block copolymer synthesized with an earlier method exhibits a crystallization-induced microphase separation.

Defect textures in concentrated fiber-filled polygonal networks in nematic liquid crystals are analyzed using differential geometry and computational modeling based on Landau--de Gennes theory. Micron fibers exhibit singular cores of strength -1/2 for odd polygons and escaped cores of strength -(N-2)/2 for even polygons (N: number of sides), in agreement with experiments while simulations predict singular cores of strength -1/2 in submicron fibers. The computed textures satisfy physical and topological stability rules, and the total charge inside each polygon obeys the Poincaré-Brouwer theorem.

We report on the phase behavior and the structure of poly(perylene bisimide acrylate), an electron accepting semiconductor polymer with disclike side-chain units, in comparison to the corresponding low molecular weight perylene bisimide. By combination of DSC, optical microscopy, and temperature-dependent small-angle and wideangle X-ray scattering, we show that both compounds display a lamello-columnar packing. While the perylene bisimide model compound crystallizes, the polymeric architecture of poly(perylene bisimide acrylate) suppresses order, leading to a 2D lamello-columnar liquid crystalline phase. The structure of the side-chain polymer in thin films with different thermal treatments as observed by GIWAXS correlates well with previously observed largely different electron mobilities. Such a polymeric, liquid crystalline compound combines the advantages of molecular order and easy processability, together with the film forming properties of polymeric materials.