Temporal Patterns of Nucleotide Misincorporations and DNA Fragmentation in Ancient DNA

DNA that survives in museum specimens, bones and other tissues recovered by archaeologists is invariably fragmented and chemically modified. The extent to which such modifications accumulate over time is largely unknown but could potentially be used to differentiate between endogenous old DNA and present-day DNA contaminating specimens and experiments. Here we examine mitochondrial DNA sequences from tissue remains that vary in age between 18 and 60,000 years with respect to three molecular features: fragment length, base composition at strand breaks, and apparent C to T substitutions. We find that fragment length does not decrease consistently over time and that strand breaks occur preferentially before purine residues by what may be at least two different molecular mechanisms that are not yet understood. In contrast, the frequency of apparent C to T substitutions towards the 5′-ends of molecules tends to increase over time. These nucleotide misincorporations are thus a useful tool to distinguish recent from ancient DNA sources in specimens that have not been subjected to unusual or harsh treatments

A formally verified compiler back-end

This article describes the development and formal verification (proof of semantic preservation) of a compiler back-end from Cminor (a simple imperative intermediate language) to PowerPC assembly code, using the Coq proof assistant both for programming the compiler and for proving its correctness. Such a verified compiler is useful in the context of formal methods applied to the certification of critical software: the verification of the compiler guarantees that the safety properties proved on the source code hold for the executable compiled code as well

Cosmic Ray Anomalies from the MSSM?

The recent positron excess in cosmic rays (CR) observed by the PAMELA satellite may be a signal for dark matter (DM) annihilation. When these measurements are combined with those from FERMI on the total ($e^++e^-$) flux and from PAMELA itself on the $\bar p/p$ ratio, these and other results are difficult to reconcile with traditional models of DM, including the conventional mSUGRA version of Supersymmetry even if boosts as large as $10^{3-4}$ are allowed. In this paper, we combine the results of a previously obtained scan over a more general 19-parameter subspace of the MSSM with a corresponding scan over astrophysical parameters that describe the propagation of CR. We then ascertain whether or not a good fit to this CR data can be obtained with relatively small boost factors while simultaneously satisfying the additional constraints arising from gamma ray data. We find that a specific subclass of MSSM models where the LSP is mostly pure bino and annihilates almost exclusively into $\tau$ pairs comes very close to satisfying these requirements. The lightest $\tilde \tau$ in this set of models is found to be relatively close in mass to the LSP and is in some cases the nLSP. These models lead to a significant improvement in the overall fit to the data by an amount $\Delta \chi^2 \sim 1/$dof in comparison to the best fit without Supersymmetry while employing boosts $\sim 100$. The implications of these models for future experiments are discussed.Comment: 57 pages, 31 figures, references adde

Fragmentation of Contaminant and Endogenous DNA in Ancient Samples Determined by Shotgun Sequencing; Prospects for Human Palaeogenomics

Despite the successful retrieval of genomes from past remains, the prospects for human palaeogenomics remain unclear because of the difficulty of distinguishing contaminant from endogenous DNA sequences. Previous sequence data generated on high-throughput sequencing platforms indicate that fragmentation of ancient DNA sequences is a characteristic trait primarily arising due to depurination processes that create abasic sites leading to DNA breaks

Decaying Dark Matter in Supersymmetric Model and Cosmic-Ray Observations

We study cosmic-rays in decaying dark matter scenario, assuming that the dark matter is the lightest superparticle and it decays through a R-parity violating operator. We calculate the fluxes of cosmic-rays from the decay of the dark matter and those from the standard astrophysical phenomena in the same propagation model using the GALPROP package. We reevaluate the preferred parameters characterizing standard astrophysical cosmic-ray sources with taking account of the effects of dark matter decay. We show that, if energetic leptons are produced by the decay of the dark matter, the fluxes of cosmic-ray positron and electron can be in good agreements with both PAMELA and Fermi-LAT data in wide parameter region. It is also discussed that, in the case where sizable number of hadrons are also produced by the decay of the dark matter, the mass of the dark matter is constrained to be less than 200-300 GeV in order to avoid the overproduction of anti-proton. We also show that the cosmic gamma-ray flux can be consistent with the results of Fermi-LAT observation if the mass of the dark matter is smaller than nearly 4 TeV.Comment: 24 pages, 5 figure

The script concordance test in radiation oncology: validation study of a new tool to assess clinical reasoning

<p>Abstract</p> <p>Background</p> <p>The Script Concordance test (SCT) is a reliable and valid tool to evaluate clinical reasoning in complex situations where experts' opinions may be divided. Scores reflect the degree of concordance between the performance of examinees and that of a reference panel of experienced physicians. The purpose of this study is to demonstrate SCT's usefulness in radiation oncology.</p> <p>Methods</p> <p>A 90 items radiation oncology SCT was administered to 155 participants. Three levels of experience were tested: medical students (n = 70), radiation oncology residents (n = 38) and radiation oncologists (n = 47). Statistical tests were performed to assess reliability and to document validity.</p> <p>Results</p> <p>After item optimization, the test comprised 30 cases and 70 questions. Cronbach alpha was 0.90. Mean scores were 51.62 (± 8.19) for students, 71.20 (± 9.45) for residents and 76.67 (± 6.14) for radiation oncologists. The difference between the three groups was statistically significant when compared by the Kruskall-Wallis test (p < 0.001).</p> <p>Conclusion</p> <p>The SCT is reliable and useful to discriminate among participants according to their level of experience in radiation oncology. It appears as a useful tool to document the progression of reasoning during residency training.</p

Analysis of Human Accelerated DNA Regions Using Archaic Hominin Genomes

Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations

An empirical investigation of the influence of collaboration in Finance on article impact

We investigate the impact of collaborative research in academic Finance literature to find out whether and to what extent collaboration leads to higher impact articles (6,667 articles across 2001-2007 extracted from the Web of Science). Using the top 5 % as ranked by the 4-year citation counts following publication, we also follow related secondary research questions such as the relationships between article impact and author impact; collaboration and average author impact of an article; and, the nature of geographic collaboration. Key findings indicate: collaboration does lead to articles of higher impact but there is no significant marginal value for collaboration beyond three authors; high impact articles are not monopolized by high impact authors; collaboration and the average author impact of high-impact articles are positively associated, where collaborative articles have a higher mean author impact in comparison to single-author articles; and collaboration among the authors of high impact articles is mostly cross-institutional