548 research outputs found

    Efficient Certified RAT Verification

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    Clausal proofs have become a popular approach to validate the results of SAT solvers. However, validating clausal proofs in the most widely supported format (DRAT) is expensive even in highly optimized implementations. We present a new format, called LRAT, which extends the DRAT format with hints that facilitate a simple and fast validation algorithm. Checking validity of LRAT proofs can be implemented using trusted systems such as the languages supported by theorem provers. We demonstrate this by implementing two certified LRAT checkers, one in Coq and one in ACL2

    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

    Analytical and numerical validation of a plate-plate tribometer for measuring wall slip

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    We model the Darmstadt Slip Length Tribometer (DSLT), specially designed to measure viscosity and slip length simultaneously for lubrication gaps in the range of approximately 10 micrometres at relevant temperatures and surface roughness. We investigate the inlet effect of the flow on the results by varying the inner radius of the fluid inlet pipe. The outcomes of numerical simulations suggest that variations in the diameter of this inner radius have minimal impact on the results. Specifically, any alterations in the velocity profile near the inlet, brought about by changes in the diameter, quickly revert to the profile predicted by the analytical model. The main conclusion drawn from this study is the validation of the Navier-Slip boundary condition as an effective model for technical surface roughness in CFD simulations and the negligible influence of the inlet effect on the fluid dynamics between the tribometer's plates

    Structure elucidation and characterization of patulin synthase, insights into the formation of a fungal mycotoxin

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    Patulin synthase (PatE) from Penicillium expansum is a flavin-dependent enzyme that catalyses the last step in the biosynthesis of the mycotoxin patulin. This secondary metabolite is often present in fruit and fruit-derived products, causing postharvest losses. The patE gene was expressed in Aspergillus niger allowing purification and characterization of PatE. This confirmed that PatE is active not only on the proposed patulin precursor ascladiol but also on several aromatic alcohols including 5-hydroxymethylfurfural. By elucidating its crystal structure, details on its catalytic mechanism were revealed. Several aspects of the active site architecture are reminiscent of that of fungal aryl-alcohol oxidases. Yet, PatE is most efficient with ascladiol as substrate confirming its dedicated role in biosynthesis of patulin.</p

    Increased sleep need and daytime sleepiness 6 months after traumatic brain injury: a prospective controlled clinical trial

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    In a controlled, prospective, electrophysiological study, Imbach et al. demonstrate increased sleep need and excessive daytime sleepiness 6 months after traumatic brain injury. Sleep is more consolidated after brain trauma, and an increase in sleep need is associated with intracranial haemorrhage. Trauma patients underestimate their increased sleep need and sleepines

    A Vinča potscape: formal chronological models for the use and development of Vinča ceramics in south-east Europe.

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    Recent work at Vinča-Belo Brdo has combined a total of more than 200 radiocarbon dates with an array of other information to construct much more precise narratives for the structural history of the site and the cultural materials recovered from it. In this paper, we present the results of a recent attempt to construct formal models for the chronology of the wider Vinča potscape, so that we can place our now detailed understanding of changes at Belo Brdo within their contemporary contexts. We present our methodology for assessing the potential of the existing corpus of more than 600 radiocarbon dates for refining the chronology of the five phases of Vinča ceramics proposed by Milojčić across their spatial ranges, including a total of 490 of them in a series of Bayesian chronological models. Then we outline our main results for the development of Vinča pottery. Finally, we discuss some of the major implications for our understanding of the source, character and tempo of material change

    GM-CSF/IL-3/IL-5 receptor common β chain (CD131) expression as a biomarker of antigen-stimulated CD8+ T cells

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    <p>Abstract</p> <p>Background</p> <p>Upon Ag-activation cytotoxic T cells (CTLs) produce IFN-γ GM-CSF and TNF-α, which deliver simultaneously pro-apoptotic and pro-inflammatory signals to the surrounding microenvironment. Whether this secretion affects in an autocrine loop the CTLs themselves is unknown.</p> <p>Methods</p> <p>Here, we compared the transcriptional profile of Ag-activated, Flu-specific CTL stimulated with the FLU M1:58-66 peptide to that of convivial CTLs expanded <it>in vitro </it>in the same culture. PBMCs from 6 HLA-A*0201 expressing donors were expanded for 7 days in culture following Flu M1:58-66 stimulation in the presence of 300 IU/ml of interleukin-2 and than sorted by high speed sorting to high purity CD8+ expressing T cells gated according to FluM1:58-66 tetrameric human leukocyte antigen complexes expression.</p> <p>Results</p> <p>Ag-activated CTLs displayed higher levels of IFN-γ, GM-CSF (CSF2) and GM-CSF/IL-3/IL-5 receptor common β- chain (CD131) but lacked completely expression of IFN-γ receptor-II and IFN-stimulated genes (ISGs). This observation suggested that Ag-activated CTLs in preparation for the release of IFN-γ and GM-CSF shield themselves from the potentially apoptotic effects of the former entrusting their survival to GM-SCF. <it>In vitro </it>phenotyping confirmed the selective surface expression of CD131 by Ag-activated CTLs and their increased proliferation upon exogenous administration of GM-CSF.</p> <p>Conclusion</p> <p>The selective responsiveness of Ag-activated CTLs to GM-CSF may provide an alternative explanation to the usefulness of this chemokine as an adjuvant for T cell aimed vaccines. Moreover, the selective expression of CD131 by Ag-activated CTLs proposes CD131 as a novel biomarker of Ag-dependent CTL activation.</p

    Lipoprotein ability to exchange and remove lipids from model membranes as a function of fatty acid saturation and presence of cholesterol

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    Lipoproteins play a central role in the development of atherosclerosis. High and low-density lipoproteins (HDL and LDL), known as 'good' and 'bad' cholesterol, respectively, remove and/or deposit lipids into the artery wall. Hence, insight into lipid exchange processes between lipoproteins and cell membranes is of particular importance in understanding the onset and development of cardiovascular disease. In order to elucidate the impact of phospholipid tail saturation and the presence of cholesterol in cell membranes on these processes, neutron reflection was employed in the present investigation to follow lipid exchange with both HDL and LDL against model membranes. Mirroring clinical risk factors for the development of atherosclerosis, lower exchange was observed in the presence of cholesterol, as well as for an unsaturated phospholipid, compared to faster exchange when using a fully saturated phospholipid. These results highlight the importance of membrane composition on the interaction with lipoproteins, chiefly the saturation level of the lipids and presence of cholesterol, and provide novel insight into factors of importance for build-up and reversibility of atherosclerotic plaque. In addition, the correlation between the results and well-established clinical risk factors suggests that the approach taken can be employed also for understanding a broader set of risk factors including, e.g., effects of triglycerides and oxidative stress, as well as local effects of drugs on atherosclerotic plaque formation

    A transcribed enhancer dictates mesendoderm specification in pluripotency.

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    Enhancers and long noncoding RNAs (lncRNAs) are key determinants of lineage specification during development. Here, we evaluate remodeling of the enhancer landscape and modulation of the lncRNA transcriptome during mesendoderm specification. We sort mesendodermal progenitors from differentiating embryonic stem cells (ESCs) according to Eomes expression, and find that enhancer usage is coordinated with mesendoderm-specific expression of key lineage-determining transcription factors. Many of these enhancers are associated with the expression of lncRNAs. Examination of ESC-specific enhancers interacting in three-dimensional space with mesendoderm-specifying transcription factor loci identifies MesEndoderm Transcriptional Enhancer Organizing Region (Meteor). Genetic and epigenetic manipulation of the Meteor enhancer reveal its indispensable role during mesendoderm specification and subsequent cardiogenic differentiation via transcription-independent and -dependent mechanisms. Interestingly, Meteor-deleted ESCs are epigenetically redirected towards neuroectodermal lineages. Loci, topologically associating a transcribed enhancer and its cognate protein coding gene, appear to represent therefore a class of genomic elements controlling developmental competence in pluripotency

    Combining Decision Procedures for Sorted Theories

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    Abstract. The Nelson-Oppen combination method combines decision procedures for theories satisfying certain conditions into a decision pro-cedure for their union. While the method is known to be correct in the setting of unsorted first-order logic, some current implementations of it appear in tools that use a sorted input language. So far, however, there have been no theoretical results on the correctness of the method in a sorted setting, nor is it obvious that the method in fact lifts as is to logics with sorts. To bridge this gap between the existing theoretical results and the current implementations, we extend the Nelson-Oppen method to (order-)sorted logic and prove it correct under conditions sim-ilar to the original ones. From a theoretical point of view, the extension is relevant because it provides a rigorous foundation for the application of the method in a sorted setting. From a practical point of view, the extension has the considerable added benefits that in a sorted setting the method’s preconditions become easier to satisfy in practice, and the method’s nondeterminism is generally reduced.
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