Bounded Determinization of Timed Automata with Silent Transitions

Deterministic timed automata are strictly less expressive than their non-deterministic counterparts, which are again less expressive than those with silent transitions. As a consequence, timed automata are in general non-determinizable. This is unfortunate since deterministic automata play a major role in model-based testing, observability and implementability. However, by bounding the length of the traces in the automaton, effective determinization becomes possible. We propose a novel procedure for bounded determinization of timed automata. The procedure unfolds the automata to bounded trees, removes all silent transitions and determinizes via disjunction of guards. The proposed algorithms are optimized to the bounded setting and thus are more efficient and can handle a larger class of timed automata than the general algorithms. The approach is implemented in a prototype tool and evaluated on several examples. To our best knowledge, this is the first implementation of this type of procedure for timed automata.Comment: 25 page

Entretien avec Bertrand Westphal

Jean-Marc Moura Dans votre récent ouvrage, La cage des méridiens (Minuit, 2016), vous écrivez : “La littérature et les arts sont appelés à tracer, à identifier des connexions qui activeraient la carte d’un monde renouvelé”. En quel sens pourrait s’opérer ce renouvellement littéraire ? Bertrand Westphal Il n’est guère original de le dire, mais tant pis : nous habitons une planète dont beaucoup de gens conservent une vision superficielle, la vision d’une surface homogénéisée bâtie sur des réfl..

A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients

International audiencen.

Arthroscopic Repair of Proximal Posterior Cruciate Ligament Injuries in Pediatric Patients.

A renewed interest in arthroscopic knee ligament repair is emerging as a result of diagnostic and technical improvements. In pediatric patients with posterior cruciate ligament (PCL) injury, surgical reconstruction is rarely considered as an option because of the risk of iatrogenic physeal injury. In this Technical Note, we describe an arthroscopic surgical repair technique of PCL proximal avulsions in pediatric patients. The main reasons to consider arthroscopic PCL repair in this population include minimal surgical morbidity, preservation of the complex biomechanical properties of the native ligament, the small diameter of the bone tunnels, the physeal respecting nature of the procedure, the absence of graft harvesting, and the absence of fixation devices. The indications for this technique are limited to patients with an acute proximal PCL avulsion. Investigation performed from at Centre Orthopédique Santy, FIFA Medical Center of Excellence, Lyon, France

Locke's legacy

A organização de um colóquio em torno da “herança de Locke” foi uma ideia que nasceu no Centro de Estudos Anglísticos da Universidade de Lisboa, no âmbito do núcleo de investigação dedicado aos estudos de cultura inglesa. Vários textos de Locke são regularmente incluídos nos programas de graduação e de pósgraduação em Estudos Anglísticos, além de objecto de estudo especializado no Centro de Estudos Anglísticos. Assim, fazia todo o sentido comemorar, no ano de 2004, a passagem de mais um centenário sobre a morte de Locke, e celebrar a vitalidade da sua obra ao longo de três séculos reunindo especialistas que, publicamente, apresentassem e discutissem aspectos dessa obra que continuam activos no presente. O volume que agora se publica reúne as comunicações apresentadas em Janeiro de 2004. A variedade dos temas abordados e a manifesta relevância de que se revestem para o estudo da modernidade demonstram que a herança de Locke continua a produzir riqueza, e que constitui património cultural a ser herdado por novas gerações.Fundação para a Ciência e a Tecnologi

How Communication and Control Processes Improve Quality

In order to achieve excellence, an organization should use two key instruments—quality and an effi cient and effective communication process amongst all employees—so it can attain quality management. This chapter aims to examine whether organizational communication and quality are interrelated, in order to answer the following question: Is it necessary to improve communication within an organization so that quality management can be effi ciently and effectively pursued? For this purpose, data were collected through the administration of a questionnaire to the staff of a Portuguese public organization. The fi ndings showed that, in this organization, communication among employees of various sectors is satisfactory and that there is mutual help between them in order to improve the organizational performance

Nanoparticle-based bioactive agent release systems for bone and cartilage tissue engineering

The inability to deliver bioactive agents locally in a transient but sustained manner is one of the challenges on the development of bio-functionalized scaffolds for tissue engineering (TE) and regenerative medicine. The mode of release is especially relevant when the bioactive agent is a growth factor (GF), because the dose and the spatiotemporal release of such agents at the site of injury are crucial to achieve a successful outcome. Strategies that combine scaffolds and drug delivery systems have the potential to provide more effective tissue regeneration relative to current therapies. Nanoparticles (NPs) can protect the bioactive agents, control its profile, decrease the occurrence and severity of side effects and deliver the bioactive agent to the target cells maximizing its effect. Scaffolds containing NPs loaded with bioactive agents can be used for their local delivery, enabling site-specific pharmacological effects such as the induction of cell proliferation and differentiation, and, consequently, neo-tissue formation. This review aims to describe the concept of combining NPs with scaffolds, and the current efforts aiming to develop highly multi-functional bioactive agent release systems, with the emphasis on their application in TE of connective tissues.POLARIS (REGPOT-CT2012-316331-POLARIS), RL3 – TECT – NORTE-01-0124-FEDER-000020, co-financed by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF), the OsteoGraphy (PTDC/EME-MFE/2008) and MaxBone (PTDC/SAU-ENB/115179/2009) project

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics.

ABSTRACT: A global genome database of all of Earth’s species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic information available. To contribute to a more complete planetary genomic database, scientists and institutions across the world have united under the Earth BioGenome Project (EBP), which plans to sequence and assemble high-quality reference genomes for all ∼1.5 million recognized eukaryotic species through a stepwise phased approach. As the initiative transitions into Phase II, where 150,000 species are to be sequenced in just four years, worldwide participation in the project will be fundamental to success. As the European node of the EBP, the European Reference Genome Atlas (ERGA) seeks to implement a new decentralised, accessible, equitable and inclusive model for producing high-quality reference genomes, which will inform EBP as it scales. To embark on this mission, ERGA launched a Pilot Project to establish a network across Europe to develop and test the first infrastructure of its kind for the coordinated and distributed reference genome production on 98 European eukaryotic species from sample providers across 33 European countries. Here we outline the process and challenges faced during the development of a pilot infrastructure for the production of reference genome resources, and explore the effectiveness of this approach in terms of high-quality reference genome production, considering also equity and inclusion. The outcomes and lessons learned during this pilot provide a solid foundation for ERGA while offering key learnings to other transnational and national genomic resource projects.info:eu-repo/semantics/publishedVersio

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life