160 research outputs found

    Termination of Rewriting with and Automated Synthesis of Forbidden Patterns

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    We introduce a modified version of the well-known dependency pair framework that is suitable for the termination analysis of rewriting under forbidden pattern restrictions. By attaching contexts to dependency pairs that represent the calling contexts of the corresponding recursive function calls, it is possible to incorporate the forbidden pattern restrictions in the (adapted) notion of dependency pair chains, thus yielding a sound and complete approach to termination analysis. Building upon this contextual dependency pair framework we introduce a dependency pair processor that simplifies problems by analyzing the contextual information of the dependency pairs. Moreover, we show how this processor can be used to synthesize forbidden patterns suitable for a given term rewriting system on-the-fly during the termination analysis.Comment: In Proceedings IWS 2010, arXiv:1012.533

    Acute induction of cell death-related IFN stimulated genes (ISG) differentiates highly from moderately virulent CSFV strains

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    Classical swine fever (CSF) severity is dependent on the virulence of the CSF virus (CSFV) strain. The earliest event detected following CSFV infection is a decrease in lymphocytes number. With some CSFV strains this leads to lymphopenia, the severity varying according to strain virulence. This lymphocyte depletion is attributed to an induction of apoptosis in non-infected bystander cells. We collected peripheral blood mononuclear cells (PBMC) before and during 3 days post-infection with either a highly or moderately virulent CSFV strain and subjected them to comparative microarray analysis to decipher the transcriptomic modulations induced in these cells in relation to strain virulence. The results revealed that the main difference between strains resided in the kinetics of host response to the infection: strong and immediate with the highly virulent strain, progressive and delayed with the moderately virulent one. Also although cell death/apoptosis-related IFN stimulated genes (ISG) were strongly up-regulated by both strains, significant differences in their regulation were apparent from the observed differences in onset and extent of lymphopenia induced by the two strains. Furthermore, the death receptors apoptotic pathways (TRAIL-DR4, FASL-FAS and TNFa-TNFR1) were also differently regulated. Our results suggest that CSFV strains might exacerbate the interferon alpha response, leading to bystander killing of lymphocytes and lymphopenia, the severity of which might be due to the host’s loss of control of IFN production and downstream effectors regulation

    One planet: one health. A call to support the initiative on a global science–policy body on chemicals and waste

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    The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientifc knowledge and data compiled and critically evaluated by an overarching science–policy inter‑ face body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems think‑ ing. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientifc networks and to intensify science–policy interaction with national governments to support the nego‑ tiations on the establishment of an intergovernmental body based on scientifc knowledge explaining the anticipated beneft for human and environmental health

    Bacillus cereus Biovar Anthracis Causing Anthrax in Sub-Saharan Africa—Chromosomal Monophyly and Broad Geographic Distribution

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    Through full genome analyses of four atypical Bacillus cereus isolates, designated B. cereus biovar anthracis, we describe a distinct clade within the B. cereus group that presents with anthrax-like disease, carrying virulence plasmids similar to those of classic Bacillus anthracis. We have isolated members of this clade from different mammals (wild chimpanzees, gorillas, an elephant and goats) in West and Central Africa (Cîte d’Ivoire, Cameroon, Central African Republic and Democratic Republic of Congo). The isolates shared several phenotypic features of both B. anthracis and B. cereus, but differed amongst each other in motility and their resistance or sensitivity to penicillin. They all possessed the same mutation in the regulator gene plcR, different from the one found in B. anthracis, and in addition, carry genes which enable them to produce a second capsule composed of hyaluronic acid. Our findings show the existence of a discrete clade of the B. cereus group capable of causing anthrax-like disease, found in areas of high biodiversity, which are possibly also the origin of the worldwide distributed B. anthracis. Establishing the impact of these pathogenic bacteria on threatened wildlife species will require systematic investigation. Furthermore, the consumption of wildlife found dead by the local population and presence in a domestic animal reveal potential sources of exposure to humans

    Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients.

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    OBJECTIVE: To foster trial-readiness of coenzyme Q8A (COQ8A)-ataxia, we map the clinicogenetic, molecular, and neuroimaging spectrum of COQ8A-ataxia in a large worldwide cohort, and provide first progression data, including treatment response to coenzyme Q10 (CoQ10). METHODS: Cross-modal analysis of a multicenter cohort of 59 COQ8A patients, including genotype-phenotype correlations, 3D-protein modeling, in vitro mutation analyses, magnetic resonance imaging (MRI) markers, disease progression, and CoQ10 response data. RESULTS: Fifty-nine patients (39 novel) with 44 pathogenic COQ8A variants (18 novel) were identified. Missense variants demonstrated a pleiotropic range of detrimental effects upon protein modeling and in vitro analysis of purified variants. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms. Multisystemic involvement was more prevalent in missense than biallelic loss-of-function variants (82-93% vs 53%; p = 0.029). Cerebellar atrophy was universal on MRI (100%), with cerebral atrophy or dentate and pontine T2 hyperintensities observed in 28%. Cross-sectional (n = 34) and longitudinal (n = 7) assessments consistently indicated mild-to-moderate progression of ataxia (SARA: 0.45/year). CoQ10 treatment led to improvement by clinical report in 14 of 30 patients, and by quantitative longitudinal assessments in 8 of 11 patients (SARA: -0.81/year). Explorative sample size calculations indicate that ≄48 patients per arm may suffice to demonstrate efficacy for interventions that reduce progression by 50%. INTERPRETATION: This study provides a deeper understanding of the disease, and paves the way toward large-scale natural history studies and treatment trials in COQ8A-ataxia. ANN NEUROL 2020;88:251-263

    Trends in obesity and diabetes across Africa from 1980 to 2014: an analysis of pooled population-based studies

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    Background: The 2016 Dar Es Salaam Call to Action on Diabetes and Other non-communicable diseases (NCDs) advocates national multi-sectoral NCD strategies and action plans based on available data and information from countries of sub-Saharan Africa and beyond. We estimated trends from 1980 to 2014 in age-standardized mean body mass index (BMI) and diabetes prevalence in these countries, in order to assess the co-progression and assist policy formulation. Methods: We pooled data from African and worldwide population-based studies which measured height, weight and biomarkers to assess diabetes status in adults aged ≄ 18 years. A Bayesian hierarchical model was used to estimate trends by sex for 200 countries and territories including 53 countries across five African regions (central, eastern, northern, southern and western), in mean BMI and diabetes prevalence (defined as either fasting plasma glucose of ≄ 7.0 mmol/l, history of diabetes diagnosis, or use of insulin or oral glucose control agents). Results: African data came from 245 population-based surveys (1.2 million participants) for BMI and 76 surveys (182 000 participants) for diabetes prevalence estimates. Countries with the highest number of data sources for BMI were South Africa (n = 17), Nigeria (n = 15) and Egypt (n = 13); and for diabetes estimates, Tanzania (n = 8), Tunisia (n = 7), and Cameroon, Egypt and South Africa (all n = 6). The age-standardized mean BMI increased from 21.0 kg/m2 (95% credible interval: 20.3–21.7) to 23.0 kg/m2 (22.7–23.3) in men, and from 21.9 kg/m2 (21.3–22.5) to 24.9 kg/m2 (24.6–25.1) in women. The age-standardized prevalence of diabetes increased from 3.4% (1.5–6.3) to 8.5% (6.5–10.8) in men, and from 4.1% (2.0–7.5) to 8.9% (6.9–11.2) in women. Estimates in northern and southern regions were mostly higher than the global average; those in central, eastern and western regions were lower than global averages. A positive association (correlation coefficient ≃ 0.9) was observed between mean BMI and diabetes prevalence in both sexes in 1980 and 2014. Conclusions: These estimates, based on limited data sources, confirm the rapidly increasing burden of diabetes in Africa. This rise is being driven, at least in part, by increasing adiposity, with regional variations in observed trends. African countries’ efforts to prevent and control diabetes and obesity should integrate the setting up of reliable monitoring systems, consistent with the World Health Organization’s Global Monitoring System Framework

    Reinterpretation of LHC Results for New Physics: Status and recommendations after Run 2

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    We report on the status of efforts to improve the reinterpretation of searches and measurements at the LHC in terms of models for new physics, in the context of the LHC Reinterpretation Forum. We detail current experimental offerings in direct searches for new particles, measurements, technical implementations and Open Data, and provide a set of recommendations for further improving the presentation of LHC results in order to better enable reinterpretation in the future. We also provide a brief description of existing software reinterpretation frameworks and recent global analyses of new physics that make use of the current data

    Gamma-ray and radio properties of six pulsars detected by the fermi large area telescope

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    We report the detection of pulsed Îł-rays for PSRs J0631+1036, J0659+1414, J0742-2822, J1420-6048, J1509-5850, and J1718-3825 using the Large Area Telescope on board the Fermi Gamma-ray Space Telescope (formerly known as GLAST). Although these six pulsars are diverse in terms of their spin parameters, they share an important feature: their Îł-ray light curves are (at least given the current count statistics) single peaked. For two pulsars, there are hints for a double-peaked structure in the light curves. The shapes of the observed light curves of this group of pulsars are discussed in the light of models for which the emission originates from high up in the magnetosphere. The observed phases of the Îł-ray light curves are, in general, consistent with those predicted by high-altitude models, although we speculate that the Îł-ray emission of PSR J0659+1414, possibly featuring the softest spectrum of all Fermi pulsars coupled with a very low efficiency, arises from relatively low down in the magnetosphere. High-quality radio polarization data are available showing that all but one have a high degree of linear polarization. This allows us to place some constraints on the viewing geometry and aids the comparison of the Îł-ray light curves with high-energy beam models
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