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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. 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 promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
- Reiersolmoen, A. C., et al.
(författare)
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Catalytic Activity of trans-Bis(pyridine)gold Complexes
- 2020
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 142:13, s. 6439-6446
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Tidskriftsartikel (refereegranskat)abstract
- Gold catalysis has become one of the fastest growing fields in chemistry, providing new organic transformations and offering excellent chemoselectivities under mild reaction conditions. Methodological developments have been driven by wide applicability in the synthesis of complex structures, whereas the mechanistic understanding of Au(III)-mediated processes remains scanty and have become the Achilles' heel of methodology development. Herein, the systematic investigation of the reactivity of bis(pyridine)-ligated Au(III) complexes is presented, based on NMR spectroscopic, X-ray crystallographic, and DFT data. The electron density of pyridines modulates the catalytic activity of Au(III) complexes in propargyl ester cyclopropanation of styrene. To avoid strain induced by a ligand with a nonoptimal nitrogen-nitrogen distance, bidentate bis(pyridine)-Au(III) complexes convert into dimers. For the first time, bis(pyridine)Au(I) complexes are shown to be catalytically active, with their reactivity being modulated by strain.
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| 7. |
- Ngaosuvan, Leonard, et al.
(författare)
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Improving Custody Dispute Negotiation: Empirical Testing of the Equality Principle
- 2020
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Ingår i: Family Court Review. - Hoboken, NJ, United States : Wiley. - 1531-2445 .- 1744-1617. ; 58:4, s. 1049-1060
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Tidskriftsartikel (refereegranskat)abstract
- The Equality Principle (EP) is a novel idea to motivate parents litigating in custody disputes to negotiate. The EP is designed for a special but common case in which both parents are individually fit, there are no decisive differences between the two households that the parents live in, but the conflict between the parents is so infected that the children's well-being is threatened and shared custody must be ruled out. The present paper empirically tested the Equality Principle in its higher bidder version. In this version, both parents are first told that the conditions for the EP are met. Then, both parents are asked how much visitation they would allow the other parent, assuming that they would win sole custody and living. The most generous parent is awarded custody and living, along with a dictum to facilitate the promised amount of visitation. In the present model (PM), the offered amount of visitation has no functional effect on the custody dispute because the judges and jurors award custody as well as the amount of visitation. A within-subjects vignette experiment measured 52 participants' levels of visitation generosity in the EP and the PM. Participants showed significantly higher visitation generosity in the EP compared to the PM. The results are discussed in terms of representation of the present model, an equal amount of visitation offered, ecological validity, child perspective, and appellant's rights. In conclusion, the present paper showed that the EP is a promising strategy to resolve seemingly unresolvable custody disputes. Practicioner's Keypoints The longer the custody dispute, the more children suffer. The Equality Principle encourages swift resolution which helps children. The Equality Principle is designed to resolve custody litigations where both parents are fit by making them compete in visitation generosity. The Equality Principle has at least two versions; randomization and highest bidder of visitation time wins. Highest bidder is probably more plausible for the general public. Empirical evidence shows that the Equality Principle in the highest bidder wins variant is a promising strategy to quickly resolve high conflict custody disputes with fit parents.
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- Woehlbrandt, Stephan, et al.
(författare)
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Permanent porosity and role of sulfonate groups in coordination networks constructed from a new polyfunctional phosphonato-sulfonate linker molecule
- 2020
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Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 49:8, s. 2724-2733
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Tidskriftsartikel (refereegranskat)abstract
- The new linker molecule (H2O3PCH2)(2)N-CH2C6H4SO3H, (4-{[bis(phosphonomethyl)amino]methyl}benzene-sulfonic acid, H5L), bearing both phosphonic and sulfonic acid groups, was employed for the synthesis of new coordination polymers (CPs). Four new CPs of composition [Mg(H3L)(H2O)(2)]H2O (1), [Mg-2(HL)(H2O)(6)]2H(2)O (2), [Ba(H3L)(H2O)]H2O (3) and [Pb-2(HL)]H2O (4), were discovered using high-throughput methods and all structures were determined by single-crystal X-ray diffraction (SCXRD). With increasing ionic radius of the metal ion, an increase in coordination number from CN = 6 (Mg2+) to CN = 9 (Ba2+) and an increase in the dimensionality of the network from 1D to 3D is observed. This is reflected in the composition of the IBU and the number of metal ions that are connected by each linker molecule, i.e. from three in 1 to ten in 4. The connection of the IBUs leads to 1D and 2D structures in 1 and 2 with non-coordinating sulfonate groups, while 3 and 4 crystallise in MOF-type structures and coordination of the sulfonate groups is observed. The compounds exhibit thermal stabilities between 200 (2) and 345 degrees C (4) as proven by variable temperature powder X-ray diffraction (VT-PXRD) measurements. Title compound 4 contains micropores of 4 x 2 angstrom and reversible H2O uptake of 50 mg g(-1) was demonstrated by vapour sorption measurements, making it the first porous metal phosphonatosulfonate. Detailed characterisation, i.e. CHNS and TG analysis as well as NMR and IR spectroscopy measurements confirm the phase purity of the title compounds.
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