609 research outputs found

    Efficient Certified Resolution Proof Checking

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    We present a novel propositional proof tracing format that eliminates complex processing, thus enabling efficient (formal) proof checking. The benefits of this format are demonstrated by implementing a proof checker in C, which outperforms a state-of-the-art checker by two orders of magnitude. We then formalize the theory underlying propositional proof checking in Coq, and extract a correct-by-construction proof checker for our format from the formalization. An empirical evaluation using 280 unsatisfiable instances from the 2015 and 2016 SAT competitions shows that this certified checker usually performs comparably to a state-of-the-art non-certified proof checker. Using this format, we formally verify the recent 200 TB proof of the Boolean Pythagorean Triples conjecture

    QRAT+: Generalizing QRAT by a More Powerful QBF Redundancy Property

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    The QRAT (quantified resolution asymmetric tautology) proof system simulates virtually all inference rules applied in state of the art quantified Boolean formula (QBF) reasoning tools. It consists of rules to rewrite a QBF by adding and deleting clauses and universal literals that have a certain redundancy property. To check for this redundancy property in QRAT, propositional unit propagation (UP) is applied to the quantifier free, i.e., propositional part of the QBF. We generalize the redundancy property in the QRAT system by QBF specific UP (QUP). QUP extends UP by the universal reduction operation to eliminate universal literals from clauses. We apply QUP to an abstraction of the QBF where certain universal quantifiers are converted into existential ones. This way, we obtain a generalization of QRAT we call QRAT+. The redundancy property in QRAT+ based on QUP is more powerful than the one in QRAT based on UP. We report on proof theoretical improvements and experimental results to illustrate the benefits of QRAT+ for QBF preprocessing.Comment: preprint of a paper to be published at IJCAR 2018, LNCS, Springer, including appendi

    Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma

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    We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC

    New Human Papilloma Virus E2 Transcription Factor Mimics: A Tripyrrole-Peptide Conjugate with Tight and Specific DNA-Recognition

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    BACKGROUND: Human papillomavirus (HPV) is the main causative agent of cervical cancer, particularly high risk strains such us HPV-16, -18 and -31. The viral encoded E2 protein acts as a transcriptional modulator and exerts a key role in viral DNA replication. Thus, E2 constitutes an attractive target for developing antiviral agents. E2 is a homodimeric protein that interacts with the DNA target through an α-helix of each monomer. However, a peptide corresponding to the DNA recognition helix of HPV-16 E2 binds DNA with lower affinity than its full-length DNA binding domain. Therefore, in an attempt to promote the DNA binding of the isolated peptide, we have designed a conjugate compound of the E2 α-helix peptide and a derivative of the antibiotic distamycin, which involves simultaneous minor- and major-groove interactions. METHODOLOGY/PRINCIPAL FINDINGS: An E2 α-helix peptide-distamycin conjugate was designed and synthesized. It was characterized by NMR and CD spectroscopy, and its DNA binding properties were investigated by CD, DNA melting and gel shift experiments. The coupling of E2 peptide with distamycin does not affect its structural properties. The conjugate improves significantly the affinity of the peptide for specific DNA. In addition, stoichiometric amounts of specific DNA increase meaningfully the helical population of the peptide. The conjugate enhances the DNA binding constant 50-fold, maintaining its specificity. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that peptide-distamycin conjugates are a promising tool to obtain compounds that bind the E2 target DNA-sequences with remarkable affinity and suggest that a bipartite major/minor groove binding scaffold can be a useful approach for therapeutic treatment of HPV infection

    Inclusive production of charged pions in p+C collisions at 158 GeV/c beam momentum

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    The production of charged pions in minimum bias p+C interactions is studied using a sample of 377000 inelastic events obtained with the NA49 detector at the CERN SPS at 158 GeV/c beam momentum. The data cover a phase space area ranging from 0 to 1.8 GeV/c in transverse momentum and from -0.1 to 0.5 in Feynman x. Inclusive invariant cross sections are given on a grid of 270 bins per charge thus offering for the first time a dense coverage of the projectile hemisphere and of the cross-over region into the target fragmentation zone.Comment: 31 pages, 30 figures, submitted to European Journal of Physic

    Rapidity and energy dependence of the electric charge correlations in A+A collisions at the SPS energies

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    Results from electric charge correlations studied with the Balance Function method in A+A collisions from 20\emph{A} to 158\emph{A} GeV are presented in two different rapidity intervals: In the mid-rapidity region we observe a decrease of the width of the Balance Function distribution with increasing centrality of the collision, whereas this effect vanishes in the forward rapidity region. Results from the energy dependence study in central Pb+Pb collisions show that the narrowing of the Balance Function expressed by the normalised width parameter \textit{W} increases with energy towards the highest SPS and RHIC energies. Finally we compare our experimental data points with predictions of several models. The hadronic string models UrQMD and HIJING do not reproduce the observed narrowing of the Balance Function. However, AMPT which contains a quark-parton transport phase before hadronization can reproduce the narrowing of the BF's width with centrality. This confirms the proposed sensitivity of the Balance Function analysis to the time of hadronization.Comment: Submitted in Phys. Rev.

    High p_T Spectra of Identified Particles Produced in Pb+Pb Collisions at 158GeV/nucleon Beam Energy

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    Transverse momentum spectra of pi^{+/-}, p, pbar, K^{+/-}, K^0_s and Lambda at midrapidity were measured at high p_T in Pb+Pb collisions at 158GeV/nucleon beam energy by the NA49 experiment. Particle yield ratios (p/pi, K/pi and Lambda/K^0_s) show an enhancement of the baryon/meson ratio for p_T>2GeV/c. The nuclear modification factor R_{CP} is extracted and compared to RHIC measurements and pQCD calculations.Comment: Quark Matter 2005 parallel section proceeding

    Multiplicity fluctuations in nuclear collisions at 158 A GeV

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    System size dependence of multiplicity fluctuations of charged particles produced in nuclear collisions at 158 A GeV was studied in the NA49 CERN experiment. Results indicate a non-monotonic dependence of the scaled variance of the multiplicity distribution with a maximum for semi-peripheral Pb+Pb interactions with number of projectile participants of about 35. This effect is not observed in a string-hadronic model of nuclear collision HIJING.Comment: Presented at "Focus on Multiplicity", 17-19 of June, Bari, Ital
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