Interpolation Properties and SAT-based Model Checking

Craig interpolation is a widespread method in verification, with important applications such as Predicate Abstraction, CounterExample Guided Abstraction Refinement and Lazy Abstraction With Interpolants. Most state-of-the-art model checking techniques based on interpolation require collections of interpolants to satisfy particular properties, to which we refer as "collectives"; they do not hold in general for all interpolation systems and have to be established for each particular system and verification environment. Nevertheless, no systematic approach exists that correlates the individual interpolation systems and compares the necessary collectives. This paper proposes a uniform framework, which encompasses (and generalizes) the most common collectives exploited in verification. We use it for a systematic study of the collectives and of the constraints they pose on propositional interpolation systems used in SAT-based model checking

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model

Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon\u27s (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits

GLAST but not least-distribution, function, genetics and epigenetics of l-glutamate transport in brain-focus on GLAST/EAAT1

Synaptically released l-glutamate, the most important excitatory neurotransmitter in the CNS, is removed from extracellular space by fast and efficient transport mediated by several transporters; the most abundant ones are EAAT1/GLAST and EAAT2/GLT1. The review first summarizes their location, functions and basic characteristics. We then look at genetics and epigenetics of EAAT1/GLAST and EAAT2/GLT1 and perform in silico analyses of their promoter regions. There is one CpG island in SLC1A2 (EAAT2/GLT1) gene and none in SLC1A3 (EAAT1/GLAST) suggesting that DNA methylation is not the most important epigenetic mechanism regulating EAAT1/GLAST levels in brain. There are targets for specific miRNA in SLC1A2 (EAAT2/GLT1) gene. We also note that while defects in EAAT2/GLT1 have been associated with various pathological states including chronic neurodegenerative diseases, very little is known on possible contributions of defective or dysfunctional EAAT1/GLAST to any specific brain disease. Finally, we review evidence of EAAT1/GLAST involvement in mechanisms of brain response to alcoholism and present some preliminary data showing that ethanol, at concentrations which may be reached following heavy drinking, can have an effect on the distribution of EAAT1/GLAST in cultured astrocytes; the effect is blocked by baclofen, a GABA-B receptor agonist and a drug potentially useful in the treatment of alcoholism. We argue that more research effort should be focused on EAAT1/GLAST, particularly in relation to alcoholism and drug addiction

Type 2 diabetes in pregnancy: Rates of fetal malformations and level of preconception care

International audienceAn observational study was performed to assess the prevalence of fetal malformations and the level of preconception care in women with Type 2 diabetes. Pregnant women with Type 2 diabetes who delivered between 2002 and 2010 were recruited to the study. The fetal malformation rate of patients with Type 2 diabetes was compared with the rate in a control group; the general population. The malformation rate was 3.2 (7.2-2.2%; p < 0.0001) greater in the diabetes group. In addition, only 4% of women with Type 2 diabetes had preconception care. Despite evidence of benefits in women receiving preconception care, patients with Type 2 diabetes do not attend for preconception counselling and the malformation rate is high

Traitement De La Peripneumonie Contagieuse Bovine Par L’oxyteTracycline Longe Action Et Transmission Experimentale de la Maladie A Partir de Bovins Traites.

La présente étude visait à évaluer l’effet de l’oxytétracycline longue action (oxytétracycline LA) dans le traitement des bovins atteints de péripneumonie contagieuse bovine (PPCB) et de déterminer le risque de transmission de la maladie à partir d’animaux traités. Une transmission expérimentale a été conduite par la mise en contact de 16 bovins cliniquement sains et séronégatifs vis-à-vis des anticorps contre M. mycoides subsp. mycoides Small Colony (MmmSC) avec 14 bovins naturellement infectés de la maladie et traités avec l’oxytétracycline LA. L’expérimentation a duré 10 mois pendant lesquels tous les animaux ont été suivis cliniquement et prélevés à intervalles réguliers pour analyses de laboratoire. Des examens post mortem ont été réalisés sur tous les animaux afin de déceler des lésions caractéristiques de PPCB et aussi de prélever des échantillons pour analyses de laboratoire. Le traitement des animaux infectés par l’oxytétracycline LA a cliniquement guéri la grande majorité d’entre eux (12/14). Tous les 14 animaux ont séroconverti et l’analyse post-mortem a montré la présence des lésions chroniques dont des séquestres pulmonaires chez 4 d’entre eux; MmmSC a été seulement isolé à partir de ces séquestres. Toutefois les 16 animaux sains mis en contact avec ces 14 animaux sont demeurés cliniquement sains durant toute la période d’expérimentation; à l’autopsie aucune lésion caractéristique de la PPCB n’a été notée et les analyses de laboratoire sont restées négatives. Les résultats de la présente étude peuvent avoir des implications importantes dans le contrôle de la PPCB en Afrique.Mots-clés: Péripneumonie contagieuse bovine - Antibiothérapie - Oxytétracycline -Transmission expérimentale - Séquestres pulmonaires - MaliThis study evaluated the effect of long-acting oxytetracycline (Oxytetracycline LA) in the treatment of cattle infested with contagious bovine pleuropneumonia (CBPP) and to determine the risk of disease transmission from animals treated. Experimental transmission was conducted by contacting 16 cattle clinically healthy and seronegative vis-à-vis the antibodies against M. mycoides subsp. mycoides Small Colony (MmmSC) 14 cattle naturally infected with the disease and treated with oxytetracycline LA. The experiment lasted 10 months during which all animals were monitored clinically and sampled at regular intervals for laboratory analysis. Post-mortem examinations were performed on all animals to detect lesions characteristic of CBPP and also take samples for laboratory analysis. The treatment of animals infected with oxytetracycline LA clinically cured a large majority of them (12/14). All 14 animals were seroconverted and post-mortem analysis showed the presence of chronic lesions including pulmonary sequestrations in 4 of them; MmmSC was only isolated from these receivers. However the 16 healthy animals in contact with these 14 animals remained clinically healthy throughout the experimental period, at autopsy no lesions characteristic of CBPP has been noted and laboratory tests were negative. The results of this study may have important implications in the control of CBPP in Africa.Keywords: Contagious bovine pleuropneumonia - Antibiotic - Oxytetracycline-Experimental transmission - Pulmonary lesions -Mal