The MC@NLO 4.0 Event Generator

This is the user's manual of MC@NLO 4.0. This package is a practical implementation, based upon the Fortran HERWIG and Herwig++ event generators, of the MC@NLO formalism, which allows one to incorporate NLO QCD matrix elements consistently into a parton shower framework. Processes available in this version include the hadroproduction of single vector and Higgs bosons, vector boson pairs, heavy quark pairs, single top, single top in association with a W, single top in association with a charged Higgs in type I or II 2HDM models, lepton pairs, and Higgs bosons in association with a W or Z. Spin correlations are included for all processes except ZZ production. This document is self-contained, but we emphasise the main differences with respect to previous versions.Comment: 36 pages, no figure

Investigations on path indexing for graph databases

Graph databases have become an increasingly popular choice for the management of the massive network data sets arising in many contemporary applications. We investigate the effectiveness of path indexing for accelerating query processing in graph database systems, using as an exemplar the widely used open-source Neo4j graph database. We present a novel path index design which supports efficient ordered access to paths in a graph dataset. Our index is fully persistent and designed for external memory storage and retrieval. We also describe a compression scheme that exploits the limited differences between consecutive keys in the index, as well as a workload-driven approach to indexing. We demonstrate empirically the speed-ups achieved by our implementation, showing that the path index yields query run-times from 2x up to 8000x faster than Neo4j. Empirical evaluation also shows that our scheme leads to smaller indexes than using general-purpose LZ4 compression. The complete stand-alone implementation of our index, as well as supporting tooling such as a bulk-loader, are provided as open source for further research and development

Increased importance of methane reduction for a 1.5 degree target

To understand the importance of methane on the levels of carbon emission reductions required to achieve temperature goals, a processed-based approach is necessary rather than reliance on the Transient Climate Response to Emissions. We show that plausible levels of methane (CH4) mitigation can make a substantial difference to the feasibility of achieving the Paris climate targets through increasing the allowable carbon emissions. This benefit is enhanced by the indirect effects of CH4 on ozone (O3). Here the differing effects of CH4 and CO2 on land carbon storage, including the effects of surface O3, lead to an additional increase in the allowable carbon emissions with CH4 mitigation. We find a simple robust relationship between the change in the 2100 CH4 concentration and the extra allowable cumulative carbon emissions between now and 2100 (0.27 ± 0.05 GtC per ppb CH4). This relationship is independent of modelled climate sensitivity and precise temperature target, although later mitigation of CH4 reduces its value and thus methane reduction effectiveness. Up to 12% of this increase in allowable emissions is due to the effect of surface ozone. We conclude early mitigation of CH4 emissions would significantly increase the feasibility of stabilising global warming below 1.5C, alongside having co-benefits for human and ecosystem health

Linking pollution, meteorology and climate change

This thesis examines the relationship between synoptic meteorology and particulate matter (PM10). PM10 is a pollutant of high interest to UK health policy (DEFRA, 2016) and this study evaluates the importance of Rossby wave breaking (RWB) on UK PM10 concentration ([PM10]). RWB can result in atmospheric blocking, which is one extreme of mid-latitude synoptic meteorological variability that favours the accumulation of PM10. This study finds significant increases (p<0.01) in UK Midlands [PM10] resulting from winter-time northeast Atlantic/ European RWB. Furthermore, this study shows that northeast Atlantic/ European RWB increases the probability of exceeding a hazardous [PM10] threshold. We have identified the Omega block as the most hazardous RWB subset, with a probability of exceeding a hazardous [PM10] threshold (0.383) over three times that for days without RWB (0.129). We have implemented a tracer framework within a Hadley centre Met-Office climate model (HADGEM3-GA4) to identify flow regimes influencing the UK throughout northeast Atlantic/European RWB events. A present-day HADGEM3-GA4 simulation, nudged to ERA-Interim reanalysis data, is used to verify the tracer framework and to identify the flow regimes influencing Omega block events. This study finds that the advection of European tracer and the accumulation of locally sourced tracer contribute to hazardous [PM10] throughout Omega block events. This study’s principal aim is to determine climatic shifts in both the frequency of synoptic meteorological conditions conducive to UK PM10 accumulation and in the corresponding flow regimes. Using a further two HADGEM3-GA4 simulations, we find a north-eastward climate shift in northeast Atlantic/ European RWB, with an overall reduction in events. Additionally, we find that uture RWB events result in significantly (p<0.01) increased European and reduced stagnant air masses within the UK. This result indicates a reduced frequency of UK [PM10] exceedances, however a tendency for increased transport of toxic particles from Europe

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms ( SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds ( a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines - in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G1 -S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1Amutant OCCC. Mol Cancer Ther; 15(7); 1472-84. Ó2016 AACR.</p

Hotspots of mutation and breakage in dog and human chromosomes

Sequencing of the dog genome allows an investigation of the location-dependent evolutionary processes that occurred since the common ancestor of primates and carnivores, ∼95 million years ago. We investigated variations in G+C nucleotide fraction and synonymous nucleotide substitution rates (Ks) across dog and human genomes. Our results show that dog genes located either in subtelomeric and pericentromeric regions, or in short synteny blocks, possess significantly elevated G+C fraction and Ks values. Human subtelomeric, but not pericentromeric, genes also exhibit these elevations. We then examined 1.048 Gb of human sequence that is likely not to have been located near a primate telomere at any time since the common ancestor of dog and human. We observed that regions of highest G+C or Ks (“hotspots”; median sizes of 0.5 or 1.3 Mb, respectively) within this sequence were preferentially segregated to dog subtelomeres and pericentromeres during the rearrangements that eventually gave rise to the extant canine karyotype. Our data cannot be accounted for solely on the basis of gradually elevating G+C fractions in subtelomeric regions as a consequence of biased gene conversion. Rather, we propose that high G+C sequences are found preferentially within dog subtelomeres as a direct consequence of chromosomal fission occurring more frequently within regions elevated in G+C

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy