22 research outputs found

    Signatures of mutational processes in human cancer.

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    All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy

    Aviation and global climate change in the 21st century

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    Aviation emissions contribute to the radiative forcing (RF) of climate. Of importance are emissions of carbon dioxide (CO2), nitrogen oxides (NOx), aerosols and their precursors (soot and sulphate), and increased cloudiness in the form of persistent linear contrails and induced-cirrus cloudiness. The recent Fourth Assessment Report (AR4) of the Intergovernmental Panel on Climate Change (IPCC) quantified aviation's RF contribution for 2005 based upon 2000 operations data. Aviation has grown strongly over the past years, despite world-changing events in the early 2000s; the average annual passenger traffic growth rate was 5.3% yr−1 between 2000 and 2007, resulting in an increase of passenger traffic of 38%. Presented here are updated values of aviation RF for 2005 based upon new operations data that show an increase in traffic of 22.5%, fuel use of 8.4% and total aviation RF of 14% (excluding induced-cirrus enhancement) over the period 2000–2005. The lack of physical process models and adequate observational data for aviation-induced cirrus effects limit confidence in quantifying their RF contribution. Total aviation RF (excluding induced cirrus) in 2005 was 55 mW m−2 (23–87 mW m−2, 90% likelihood range), which was 3.5% (range 1.3–10%, 90% likelihood range) of total anthropogenic forcing. Including estimates for aviation-induced cirrus RF increases the total aviation RF in 2005–78 mW m−2 (38–139 mW m−2, 90% likelihood range), which represents 4.9% of total anthropogenic forcing (2–14%, 90% likelihood range). Future scenarios of aviation emissions for 2050 that are consistent with IPCC SRES A1 and B2 scenario assumptions have been presented that show an increase of fuel usage by factors of 2.7–3.9 over 2000. Simplified calculations of total aviation RF in 2050 indicate increases by factors of 3.0–4.0 over the 2000 value, representing 4–4.7% of total RF (excluding induced cirrus). An examination of a range of future technological options shows that substantive reductions in aviation fuel usage are possible only with the introduction of radical technologies. Incorporation of aviation into an emissions trading system offers the potential for overall (i.e., beyond the aviation sector) CO2 emissions reductions. Proposals exist for introduction of such a system at a European level, but no agreement has been reached at a global level
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