On the Uniform Random Generation of Non Deterministic Automata Up to Isomorphism

In this paper we address the problem of the uniform random generation of non deterministic automata (NFA) up to isomorphism. First, we show how to use a Monte-Carlo approach to uniformly sample a NFA. Secondly, we show how to use the Metropolis-Hastings Algorithm to uniformly generate NFAs up to isomorphism. Using labeling techniques, we show that in practice it is possible to move into the modified Markov Chain efficiently, allowing the random generation of NFAs up to isomorphism with dozens of states. This general approach is also applied to several interesting subclasses of NFAs (up to isomorphism), such as NFAs having a unique initial states and a bounded output degree. Finally, we prove that for these interesting subclasses of NFAs, moving into the Metropolis Markov chain can be done in polynomial time. Promising experimental results constitute a practical contribution.Comment: Frank Drewes. CIAA 2015, Aug 2015, Umea, Sweden. Springer, 9223, pp.12, 2015, Implementation and Application of Automata - 20th International Conferenc

Apolipoprotein AIV gene variant S347 is associated with increased risk of coronary heart disease and lower plasma apolipoprotein AIV levels

The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective coronary heart disease (CHD) risk was examined in healthy UK men. Of the 2808 men followed over 9 years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [hazard ratio (HR) of 2.07 (95%CI 1.04 to 4.12)], whereas men homozygous for APOC3 1100T were protected [HR 0.28 (95%CI 0.09 to 0.87)]. In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factors APOA4 T347S alone remained in the model. Using all nine SNPs, the highest risk-estimate haplotypes carried APOA4 S347 and rare alleles of the two flanking intergenic markers. The protective effect of APOC3 1100T could be explained by negative linkage disequilibrium with these alleles. To determine the association of APOA4 T347S with apoAIV levels, the relationship was examined in 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.64±0.59 mg/dL) compared with carriers of the T347 allele (14.90±0.12 mg/dL) (P=0.035). These results demonstrate that genetic variation in and around APOA4, independent of the effects of triglyceride, is associated with risk of CHD and apoAIV levels, supporting an antiatherogenic role for apoAIV

The T allele of the hepatic lipase promoter variant C-480T is associated with increased fasting lipids and HDL and increased preprandial and postprandial LpCIII:B : European Atherosclerosis Research Study (EARS) II

The common C-480T transition in the hepatic lipase (HL) promoter has been shown to be associated with lower HL activity and increased high density lipoprotein (HDL) cholesterol. We examined the frequency and lipid associations of this HL polymorphism in 385 healthy, young (18- to 28-year-old) men whose fathers had had a premature myocardial infarction (designated cases) and 405 age-matched controls. These individuals were participants in the European Atherosclerosis Research Study II postprandial trial, who had been recruited from 11 European countries in 4 regions (the Baltic; United Kingdom; and central and southern Europe). Overall, the frequency of the T allele was 0.207 in controls and 0.244 in cases (P=0.08). The T allele was associated with higher fasting plasma total cholesterol (P<0.01), triglycerides (P<0.01), and HDL cholesterol (P<0.01). The strongest association was found with apolipoprotein (apo) A-I concentration, which was 10% higher in individuals homozygous for the T allele compared with those homozygous for the C allele (P<0.001). This polymorphism had no effect on the rise in plasma triglyceride levels after a fatty meal. However, before and after the fat load was ingested, levels of particles containing both apoC-III and apoB (LpC-III:B) were higher in carriers of the T allele, with homozygotes having 23% and 27% higher levels preprandially and postprandially, respectively, than those homozygous for the C allele (P<0.05). Thus, our results demonstrate that the C-480T polymorphism in the HL promoter is associated with alterations in plasma lipids and lipoproteins and the accumulation of atherogenic LpC-III:B particles

The Utility of Repeat Endoscopic Ultrasound-Guided Fine Needle Aspiration for Suspected Pancreatic Cancer

Background. The utility of repeat EUS in patients with suspicion for pancreatic cancer after non-diagnostic EUS-FNA study is not well established. Aim. Determine the accuracy of repeat EUS-FNA in patients with suspected pancreatic cancer and prior non-diagnostic EUS-FNA. Methods. Retrospective cohort study. Results. From 2002 to 2008 in our institution 28 patients underwent repeat EUS-FNA for suspected pancreatic cancer. Initial EUS showed a pancreatic mass in 24 (85.71%), no mass in 3 (10.71%) and possible mass in 1 (3.58%). FNA was performed and was negative for malignancy in all patients. Repeat EUS showed pancreatic mass in 27 patients (96.42%) and no mass in 1 (3.58%). FNA was performed in all patients and cytology was positive for malignancy in 6 (21.43%). Out of the 28 patients, 17 (60.71%) were eventually confirmed to have cancer. Overall repeat EUS-FNA correctly determined the true final status in 17 out of 28 patients providing sensitivity for the diagnosis of cancer of 35% (95% CI 14%–62%), specificity 100% (95% CI 72%–100%), and overall accuracy of 61%, (95% CI 28%–72%). Conclusion. Repeat EUS-FNA provides reasonable accuracy and may be worthwhile in patients with suspected pancreatic cancer who had had prior negative EUS-FNA

Genetics and beyond - the transcriptome of human monocytes and disease susceptibility

BACKGROUND: Variability of gene expression in human may link gene sequence variability and phenotypes; however, non-genetic variations, alone or in combination with genetics, may also influence expression traits and have a critical role in physiological and disease processes. METHODOLOGY/PRINCIPAL FINDINGS: To get better insight into the overall variability of gene expression, we assessed the transcriptome of circulating monocytes, a key cell involved in immunity-related diseases and atherosclerosis, in 1,490 unrelated individuals and investigated its association with >675,000 SNPs and 10 common cardiovascular risk factors. Out of 12,808 expressed genes, 2,745 expression quantitative trait loci were detected (P<5.78x10(-12)), most of them (90%) being cis-modulated. Extensive analyses showed that associations identified by genome-wide association studies of lipids, body mass index or blood pressure were rarely compatible with a mediation by monocyte expression level at the locus. At a study-wide level (P<3.9x10(-7)), 1,662 expression traits (13.0%) were significantly associated with at least one risk factor. Genome-wide interaction analyses suggested that genetic variability and risk factors mostly acted additively on gene expression. Because of the structure of correlation among expression traits, the variability of risk factors could be characterized by a limited set of independent gene expressions which may have biological and clinical relevance. For example expression traits associated with cigarette smoking were more strongly associated with carotid atherosclerosis than smoking itself. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the monocyte transcriptome is a potent integrator of genetic and non-genetic influences of relevance for disease pathophysiology and risk assessment