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

Treatment of cheese whey wastewater by combined electrochemical processes

This study shows the good performance of a sequential electrochemical methodology, consisting in electrocoagulation (EC) followed by an electrochemical advanced oxidation process (EAOP), to treat raw cheese whey wastewater at laboratory and pre-pilot scales. In EC, different electrode materials like Fe, Al and stainless steel (AISI 304 and ASI 316L) were tested. Among EAOPs, photoelectro-Fenton (PEF) and electrochemical oxidation (EO) with active anodes like Pt or DSA((R)) and non-active ones like boron-doped diamond (BDD) were studied. At both scales, the optimum anode/cathode combination in EC was Fe/AISI 304, which yielded the highest total organic carbon (TOC) removal of 22.0-27.0%. This is due to various effects on organic compounds: (i) coagulation promoted by Fe(OH)(3) flocs, (ii) cathodic reduction, and (iii) oxidation with generated active chlorine. At small scale, the resulting wastewater was further treated by PEF at pH 3.0. The highest TOC removal was achieved using the BDD, owing to the great oxidation power of hydroxyl radicals. In contrast, total nitrogen was abated much more rapidly with active anodes because of the attack of active chlorine on N-compounds. At pre-pilot scale, the post-treatment of conditioned wastewater made by EO with a BDD/Pt flow cell combined with UVA irradiation yielded the highest TOC removal, i.e., 49.1%. The high energy consumed by the UVA lamp would be a drawback at industrial scale, which could be overcome by using sunlight

Sleep on it, but only if it is difficult:effects of sleep on problem solving

Previous research has shown that performance on problem solving improves over a period of sleep compared to wakefulness. However, these studies have not determined whether sleep is beneficial for problem solving or whether sleep merely mitigates against interference due to an interruption to solution attempts. Sleep-dependent improvements have been described in terms of spreading-activation, which raises the prediction that an effect of sleep should be greater for problems requiring a broader solution search. We presented participants with a set of remote associates tasks that varied in difficulty as a function of the strength of the stimuli-answer associations. After a period of sleep, wake, or no-delay, participants reattempted previously unsolved problems. The sleep group solved more difficult problems than the other groups, but no difference was found for easy problems. We conclude that sleep facilitates problem solving, most likely via spreading activation, but this has its primary effect for harder problem

The evolution patterns of temperature, pH, and voltage during the removal of chemical oxygen demand from a landfill leachate using electrocoagulation under different conditions

In this study, electrocoagulation was evaluated for landfill leachate as a complex wastewater. Effects of all significant parameters including inter-electrode gap, current density, electrode material, time, pH, electrode numbers, salinity, and concentration were investigated. This study reports the changing patterns for chemical xxygen demand (COD) removal, temperature, voltage, and pH during EC for both Fe and Al electrodes under different conditions. According to the results, the best COD removals were achieved at shortest inter-electrode distance (0.5 cm), highest current density (1000 A m−2), highest number of electrodes (6 plates), longest time (60 min), and within acidic pH. Furthermore, for different NaCl concentrations (0–16 g l−1), both falling and rising patterns were observed. This study also provides separate results for the effect of operational parameters on pH, voltage, temperature, and energy consumption during EC. With higher inter-electrode distances, voltage and temperature rose to larger values, whereas pH fell. Besides, increases in initial pH caused rises in all voltage, temperature and pH parameters during EC. Experiments also displayed that higher values of voltage, temperature, and pH occurred at larger current densities. Additionally, with time, pH increased to more basic measures, and voltage similarly increased. Results also reported that although addition of NaCl into medium could drop the voltage and temperature, it formed both falling and rising patterns for pH at different NaCl concentrations. Plus, according to the results, voltage, temperature, and pH all experienced rising patterns in accordance with the increase in the number of electrodes. Finally, a comparative study of energy consumption was performed to analyse the operation parametric effect.Accepted Author ManuscriptBT/Environmental Biotechnolog