30 research outputs found

    Model Checking Contest @ Petri Nets, Report on the 2013 edition

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    This document presents the results of the Model Checking Contest held at Petri Nets 2013 in Milano. This contest aimed at a fair and experimental evaluation of the performances of model checking techniques applied to Petri nets. This is the third edition after two successful editions in 2011 and 2012. The participating tools were compared on several examinations (state space generation and evaluation of several types of formul{\ae} -- reachability, LTL, CTL for various classes of atomic propositions) run on a set of common models (Place/Transition and Symmetric Petri nets). After a short overview of the contest, this paper provides the raw results from the contest, model per model and examination per examination. An HTML version of this report is also provided (http://mcc.lip6.fr).Comment: one main report (422 pages) and two annexes (1386 and 1740 pages

    Spectroscopic Studies of the Iron and Manganese Reconstituted Tyrosyl Radical in Bacillus Cereus Ribonucleotide Reductase R2 Protein

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    Ribonucleotide reductase (RNR) catalyzes the rate limiting step in DNA synthesis where ribonucleotides are reduced to the corresponding deoxyribonucleotides. Class Ib RNRs consist of two homodimeric subunits: R1E, which houses the active site; and R2F, which contains a metallo cofactor and a tyrosyl radical that initiates the ribonucleotide reduction reaction. We studied the R2F subunit of B. cereus reconstituted with iron or alternatively with manganese ions, then subsequently reacted with molecular oxygen to generate two tyrosyl-radicals. The two similar X-band EPR spectra did not change significantly over 4 to 50 K. From the 285 GHz EPR spectrum of the iron form, a g1-value of 2.0090 for the tyrosyl radical was extracted. This g1-value is similar to that observed in class Ia E. coli R2 and class Ib R2Fs with iron-oxygen cluster, suggesting the absence of hydrogen bond to the phenoxyl group. This was confirmed by resonance Raman spectroscopy, where the stretching vibration associated to the radical (C-O, ν7a = 1500 cm−1) was found to be insensitive to deuterium-oxide exchange. Additionally, the 18O-sensitive Fe-O-Fe symmetric stretching (483 cm−1) of the metallo-cofactor was also insensitive to deuterium-oxide exchange indicating no hydrogen bonding to the di-iron-oxygen cluster, and thus, different from mouse R2 with a hydrogen bonded cluster. The HF-EPR spectrum of the manganese reconstituted RNR R2F gave a g1-value of ∼2.0094. The tyrosyl radical microwave power saturation behavior of the iron-oxygen cluster form was as observed in class Ia R2, with diamagnetic di-ferric cluster ground state, while the properties of the manganese reconstituted form indicated a magnetic ground state of the manganese-cluster. The recent activity measurements (Crona et al., (2011) J Biol Chem 286: 33053–33060) indicates that both the manganese and iron reconstituted RNR R2F could be functional. The manganese form might be very important, as it has 8 times higher activity

    Vitamin D and the risk of dystocia: A case-control study.

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    BackgroundDystocia is one of the most common causes of cesarean section in nulliparous women. Studies have described the presence of vitamin D receptors in the myometrium, but it is still unclear whether vitamin D affects the contractility of the smooth muscles. We therefore aimed to determine the association between the vitamin D serum level at labor and the risk of dystocia.MethodWe conducted a case-control study between January 2012 and June 2017. Cases were primiparous women, with spontaneous onset of labor, who gave birth by cesarean section due to dystocia. Controls were primiparous women with a spontaneous vaginal delivery. We included 60 women (30 cases and 30 controls) in the analysis. The differences between cases and controls were assessed using chi-squared test for categorical variables and two-sample t-test or unequal t-test for continuous variables, as appropriate, after evaluation of whether they followed the normal distributions.ResultsThe mean serum 25-hydroxyvitamin D concentrations were 53.1nmol/l (95%CI; 45.2 to 60.9) among cases and 69.9nmol/l (95%CI; 57.5 to 82.4) among controls (P = 0.02). The mean plasma parathyroid hormone levels were 2.25 pmol/l and 2.38, respectively (P = 0.57). Even though 78% of all women reported taking a minimum of 10μg/day of vitamin D throughout pregnancy, 43% had vitamin D insufficiency, defined as serum 25-hydroxyvitamin D levels below 50nmol/l.ConclusionsIn a Danish group of women having a cesarean section due to dystocia, we found decreased vitamin D levels

    Seasonal variation of dystocia in a large Danish cohort.

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    BACKGROUND: Dystocia is one of the most frequent causes of cesarean delivery in nulliparous women. Despite this, its causes are largely unknown. Vitamin D receptor (VDR) has been found in the myometrium. Thus, it is possible that vitamin D affects the contractility of the myometrium and may be involved in the pathogenesis of dystocia. Seasonal variation of dystocia in areas with distinct seasonal variation in sunlight exposure, like Denmark, could imply that vitamin D may play a role. This study examined whether there was seasonal variation in the incidence of dystocia in a Danish population. METHOD: We used information from a cohort of 34,261 nulliparous women with singleton pregnancies, spontaneous onset of labor between 37 and 42 completed gestational weeks, and vertex fetal presentation. All women gave birth between 1992 and 2010 at the Department of Obstetrics and Gynecology, Aarhus University Hospital, Skejby. Logistic regression combined with cubic spline was used to estimate the seasonal variation for each outcome after adjusting for calendar time. RESULTS: No evidence for seasonal variation was found for any of the outcomes: acute cesarean delivery due to dystocia (p = 0.44); instrumental vaginal delivery due to dystocia (p = 0.69); oxytocin augmentation due to dystocia (p = 0.46); and overall dystocia (p = 0.91). CONCLUSION: No seasonal variation in the incidence of dystocia was observed in a large cohort of Danish women. This may reflect no association between vitamin D and dystocia, or alternatively that other factors with seasonal variation and influence on the occurrence of dystocia attenuate such an association

    Seasonal variation of dystocia.

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    <p>The solid line represents the estimated seasonal variation of dystocia after adjusting for time-trend, with 95% CI (dashed line). Dots represent the relative risk (RR) obtained by grouping the season into months. Some monthly point estimates (dots) are outside the CIs of the seasonal variation curve, and one is significant, (marked with a triangle).</p

    Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis

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    Abstract Background Ankylosing spondylitis (AS) results from the combined effects of susceptibility genes and environmental factors. Polymorphisms in genes regulating inflammation may explain part of the heritability of AS. Methods Using a candidate gene approach in this case-control study, 51 mainly functional single nucleotide polymorphisms (SNPs) in genes regulating inflammation were assessed in 709 patients with AS and 795 controls. Data on the patients with AS were obtained from the DANBIO registry where patients from all of Denmark are monitored in routine care during treatment with conventional and biologic disease modifying anti-rheumatic drugs (bDMARDs). The results were analyzed using logistic regression (adjusted for age and sex). Results Nine polymorphisms were associated with risk of AS (p  A (rs1800629), and − 238 G > A (rs361525); TNFRSF1A -609 G > T (rs4149570), and PTPN22 1858 G > A (rs2476601)), b: the IL23/IL17 pathway (IL23R G > A (rs11209026), and IL18–137 G > C (rs187238)), or c: the NFkB pathway (TLR1 743 T > C (rs4833095), TLR4 T > C (rs1554973), and LY96–1625 C > G (rs11465996)). After Bonferroni correction the homozygous variant genotype of TLR1 743 T > C (rs4833095) (odds ratios (OR): 2.59, 95% confidence interval (CI): 1.48–4.51, p = 0.04), and TNFRSF1A -609 G > T (rs4149570) (OR: 1.79, 95% CI: 1.31–2.41, p = 0.01) were associated with increased risk of AS and the combined homozygous and heterozygous variant genotypes of TNF -308 G > A (rs1800629) (OR: 0.56, 95% CI: 0.44–0.72, p = 0.0002) were associated with reduced risk of AS. Conclusion We replicated associations between AS and the polymorphisms in TNF (rs1800629), TNFRSF1A (rs4149570), and IL23R (rs11209026). Furthermore, we identified novel risk loci in TNF (rs361525), IL18 (rs187238), TLR1 (rs4833095), TLR4 (rs1554973), and LY96 (rs11465996) that need validation in independent cohorts. The results suggest that genetically determined high activity of the TNF-α, IL23/IL17, and NFkB pathways increase risk of AS
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