55 research outputs found
Advances in Understanding Merocyanine based Organic Solar Cells – From the Molecular Level to the Device Level –
Gene conversion in human rearranged immunoglobulin genes
Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Comprehensive miRNA sequence analysis reveals survival differences in diffuse large B-cell lymphoma patients
Recommended from our members
Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer
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
Determination of the optical constants of bulk heterojunction active layers from standard solar cell measurements
The determination of the optical constants n(k) and k(k) for organic bulk heterojunction (BHJ) active layers from standard solar cell measurements is presented. We show for a small molecule based as well as for polymer solar cells that the complex refractive index can be derived from the external quantum efficiency (EQE) in combination with current-voltage curves obtained from a series of devices with different active layer thicknesses. The results are compared to those obtained via established techniques and the impact of differences in n(k) and k(k) on the solar cells is shown by simulation of the current density using a transfer matrix model. (C) 2014 Elsevier B.V. All rights reserved
Comparative Studies on Optical, Redox, and Photovoltaic Properties of a Series of D-A-D and Analogous D-A Chromophores
A series of new symmetrical donor-acceptor-donor (D-A-D) dyes based on s-indacene-1,3,5,7(2H,6H)-tetraone as an acceptor unit containing varying electron donating moieties and analogous donor-acceptor (D-A) chromophores with indane-1,3-dione as an acceptor are synthesized. By employing these two sets of dyes, the influence of a scaffold change from unsymmetric push-pull (D-A) to symmetrical (D-A-D) systems on optical, electrochemical, and photovoltaic properties are explored. Detailed comparative studies reveal favorable optical characteristics and considerably decreased bandgaps for the D-A-D dyes compared to those of the reference D-A chromophores. Accordingly, the evaluation of the present dyes as donor materials in bulk heterojunction (BHJ) solar cells in combination with fullerene derivatives PC61BM or PC71BM as acceptors afforded significantly improved performance for devices based on D-A-D blends (up to a factor of 4 compared to the respective D-A reference) with power conversion efficiencies of up to 2.8%. In less polar solvents such as toluene, some of the novel D-A-D chromophores exhibit unexpectedly high fluorescence quantum yields phi(em) of up to unity, in striking contrast to their weakly fluorescent D-A counterparts
Polythiophenoazomethines - alternate photoactive materials for organic photovoltaics
Solution-processable polyazomethines containing thiophenes were synthesized and used as the donor material in bulk heterojunction solar cells. The blue polymers exhibited similar electrochemical properties to the benchmark P3HT with the advantage of absorbing more of the visible spectrum. The resulting photovoltaic devices using polyazomethines in the photoactive layer with PC60BM as the acceptor showed power conversion efficiencies up to 0.22% under simulated 100 mW cm(-2) AM 1.5G irradiation. The low efficiencies are ascribed to poor charge generation because of too coarse bulk heterojunction morphology formation
NIR-Absorbing Merocyanine Dyes for BHJ Solar Cells
We have synthesized a series of new, polymethine chain extended merocyanine dyes 1-4 bearing varied acceptor units and an aminothiophene donor moiety. The optical and electronic properties of these new merocyanines have been studied in comparison with their corresponding lower homologues 5-8, which contain two methine groups less, by UV-vis and electro-optical absorption (EOA) spectroscopy and cyclic voltammetry. The absorption spectra of pi-extended merocyanines are markedly red-shifted, and their extinction coefficients are significantly increased compared to those of their lower homologues. The photovoltaic characteristics of these dyes have been explored in devices using them as donor and PC61BM fullerene as acceptor materials. Our detailed studies reveal that, despite more favorable absorption properties, the it-extended merocyanines exhibit lower short-circuit current densities (J(SC)) as well as decreased open-circuit voltages (V-OC) and power conversion efficiencies (PCE) compared with those of their respective lower homologues. The unexpected decreased J(SC) values could be explained in terms of looser packing features of pi-extended chromophores in the solid state as revealed by single-crystal X-ray analysis of two pairs (1/S and 4/8) of these dyes. By optimization of device setup PCE of 2.3% has been achieved with the Jr-extended donor material 4
- …