On the Impact of Modal Depth in Epistemic Planning (Extended Version)

Epistemic planning is a variant of automated planning in the framework of dynamic epistemic logic. In recent works, the epistemic planning problem has been proved to be undecidable when preconditions of events can be epistemic formulas of arbitrary complexity , and in particular arbitrary modal depth. It is known however that when preconditions are propositional (and there are no postconditions), the problem is between Pspace and Expspace. In this work we bring two new pieces to the picture. First, we prove that the epistemic planning problem with propositional preconditions and without postconditions is in Pspace, and is thus Pspace-complete. Second, we prove that very simple epistemic preconditions are enough to make the epistemic planning problem undecidable: preconditions of modal depth at most two suffice

Less effective selection leads to larger genomes

International audienceThe evolutionary origin of the striking genome size variations found in eukaryotes remains enigmatic. The effective size of populations, by controlling selection efficacy, is expected to be a key parameter underlying genome size evolution. However, this hypothesis has proved difficult to investigate using empirical datasets. Here, we tested this hypothesis using twenty-two de novo transcriptomes and low-coverage genomes of asellid isopods, which represent eleven independent habitat shifts from surface water to resource-poor groundwater. We show that these habitat shifts are associated with higher transcriptome-wide dN/dS. After ruling out the role of positive selection and pseudogenization, we show that these transcriptome-wide dN/dS increases are the consequence of a reduction in selection efficacy imposed by the smaller effective population size of subterranean species. This reduction is paralleled by an important increase in genome size (25% increase on average), an increase also confirmed in subterranean decapods and mollusks. We also control for an adaptive impact of genome size on life history traits but find no correlation between body size, or growth rate, and genome size. We show instead that the independent increases in genome size measured in subterranean isopods are the direct consequence of increasing invasion rates by repeated elements, which are less efficiently purged out by purifying selection. Contrary to selection efficacy, polymorphism is not correlated to genome size. We propose that recent demographic fluctuations and the difficulty to observe polymorphism variations in polymorphism-poor species can obfuscate the link between effective population size and genome size when polymorphism data is used alone

Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy

Lentiviral vector genomic RNA requires sequences that partially overlap wild-type HIV-1 gag and env genes for packaging into vector particles. These HIV-1 packaging sequences constitute 19.6% of the wild-type HIV-1 genome and contain functional cis elements that potentially compromise clinical safety. Here, we describe the development of a novel lentiviral vector (LTR1) with a unique genomic structure designed to prevent transfer of HIV-1 packaging sequences to patient cells, thus reducing the total HIV-1 content to just 4.8% of the wildtype genome. This has been achieved by reconfiguring the vector to mediate reverse-transcription with a single strand transfer, instead of the usual two, and in which HIV-1 packaging sequences are not copied. We show that LTR1 vectors offer improved safety in their resistance to remobilization in HIV-1 particles and reduced frequency of splicing into human genes. Following intravenous luciferase vector administration to neonatal mice, LTR1 sustained a higher level of liver transgene expression than an equivalent dose of a standard lentivirus. LTR1 vectors produce reverse-transcription products earlier and start to express transgenes significantly quicker than standard lentiviruses after transduction. Finally, we show that LTR1 is an effective lentiviral gene therapy vector as demonstrated by correction of a mouse hemophilia B model

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Complexité théorique du raisonnement en logique épistémique dynamique et étude d’une approche symbolique

We study the theoretical complexity of reasoning tasks involving knowledge in multi-agent systems. We consider dynamic epistemic logic (DEL) as a natural way of expressing knowledge, which allows to express nested knowledge of agents and partially observed dynamic actions. We show complexity results for model checking and satisfiability of DEL formulas, and define a symbolic approach for these problems. We also study DEL-based planning and quantification over specific actions: public announcements.Nous étudions la complexité théorique de tâches de raisonnement mettant en jeu la connaissance des agents dans les systèmes multi-agents. Nous considérons la logique épistémique dynamique (DEL) comme une façon naturelle d'exprimer la connaissance, qui permet d'exprimer la connaissance d'ordre supérieur des agents et des actions dynamiques partiellement observées. Nous montrons des résultats de complexité algorithmique pour la vérification de modèles et la satisfiabilité de formules de DEL, et définissons une approche symbolique pour ces mêmes problèmes. Nous étudions également la planification basée sur DEL ainsi que des quantifications sur certaines actions : les annonces publiques

Theoretical complexity of reasoning in dynamicepistemic logic and study of a symbolic approach

Nous étudions la complexité théorique de tâches de raisonnement mettant en jeu la connaissance des agents dans les systèmes multi-agents. Nous considérons la logique épistémique dynamique (DEL) comme une façon naturelle d'exprimer la connaissance, qui permet d'exprimer la connaissance d'ordre supérieur des agents et des actions dynamiques partiellement observées. Nous montrons des résultats de complexité algorithmique pour la vérification de modèles et la satisfiabilité de formules de DEL, et définissons une approche symbolique pour ces mêmes problèmes. Nous étudions également la planification basée sur DEL ainsi que des quantifications sur certaines actions : les annonces publiques.We study the theoretical complexity of reasoning tasks involving knowledge in multi-agent systems. We consider dynamic epistemic logic (DEL) as a natural way of expressing knowledge, which allows to express nested knowledge of agents and partially observed dynamic actions. We show complexity results for model checking and satisfiability of DEL formulas, and define a symbolic approach for these problems. We also study DEL-based planning and quantification over specific actions: public announcements

Complexité théorique du raisonnement en logique épistémique dynamique et étude d’une approche symbolique

We study the theoretical complexity of reasoning tasks involving knowledge in multi-agent systems. We consider dynamic epistemic logic (DEL) as a natural way of expressing knowledge, which allows to express nested knowledge of agents and partially observed dynamic actions. We show complexity results for model checking and satisfiability of DEL formulas, and define a symbolic approach for these problems. We also study DEL-based planning and quantification over specific actions: public announcements.Nous étudions la complexité théorique de tâches de raisonnement mettant en jeu la connaissance des agents dans les systèmes multi-agents. Nous considérons la logique épistémique dynamique (DEL) comme une façon naturelle d'exprimer la connaissance, qui permet d'exprimer la connaissance d'ordre supérieur des agents et des actions dynamiques partiellement observées. Nous montrons des résultats de complexité algorithmique pour la vérification de modèles et la satisfiabilité de formules de DEL, et définissons une approche symbolique pour ces mêmes problèmes. Nous étudions également la planification basée sur DEL ainsi que des quantifications sur certaines actions : les annonces publiques

Complexité théorique du raisonnement en logique épistémique dynamique et étude d’une approche symbolique

We study the theoretical complexity of reasoning tasks involving knowledge in multi-agent systems. We consider dynamic epistemic logic (DEL) as a natural way of expressing knowledge, which allows to express nested knowledge of agents and partially observed dynamic actions. We show complexity results for model checking and satisfiability of DEL formulas, and define a symbolic approach for these problems. We also study DEL-based planning and quantification over specific actions: public announcements.Nous étudions la complexité théorique de tâches de raisonnement mettant en jeu la connaissance des agents dans les systèmes multi-agents. Nous considérons la logique épistémique dynamique (DEL) comme une façon naturelle d'exprimer la connaissance, qui permet d'exprimer la connaissance d'ordre supérieur des agents et des actions dynamiques partiellement observées. Nous montrons des résultats de complexité algorithmique pour la vérification de modèles et la satisfiabilité de formules de DEL, et définissons une approche symbolique pour ces mêmes problèmes. Nous étudions également la planification basée sur DEL ainsi que des quantifications sur certaines actions : les annonces publiques