A procedure for splitting data-aware processes and its application to coordination

We present a procedure for splitting processes in a process algebra with multiactions and data (the untimed subset of the specification language mCRL2). This splitting procedure cuts a process into two processes along a set of actions A: Roughly, one of these processes contains no actions from A, while the other process contains only actions from A. We state and prove a theorem asserting that the parallel composition of these two processes is provably equal from a set of axioms (sound and complete with respect to strong bisimilarity) to the original process under some appropriate notion of synchronization. We apply our splitting procedure to the process algebraic semantics of the coordination language Reo: Using this procedure and its related theorem, we formally establish the soundness of splitting Reo connectors along the boundaries of their (a)synchronous regions in implementations of Reo

Ventilation practices in extremely low birth weight infants

Introdução: As práticas ventilatórias nos recém-nascidos de extremo baixo peso (RNEBP) têm vindo a alterar-se ao longo dos anos, havendo uma preocupação crescente em implementar estratégias protetoras do pulmão. O presente trabalho pretendeu caracterizar a prática ventilatória nos RNEBP numa unidade de cuidados intensivos neonatais. Métodos: Análise retrospetiva dos registos clínicos dos RNEBP, admitidos entre 01/09/2010 e 31/08/2013. Resultados: Foram admitidos 94 RNEBP (mediana peso 790 g), com idade gestacional de 23-32 semanas (mediana 27 semanas). Foi administrado pelo menos um ciclo de corticoide pré-natal em 65% e 69% receberam no mínimo uma dose de surfatante. Realizaram ventilação invasiva 74%, a maioria desde o nascimento, e 15% necessitaram de ventilação de alta frequência como resgate. Efetuaram ventilação não invasiva 70%, de forma exclusiva em 23% dos casos. Não precisaram de qualquer suporte ventilatório 3%. A mortalidade atingiu 31% (mediana idade gestacional 25 semanas), ocorrendo quase metade dos óbitos no primeiro dia de vida. Desenvolveram hemorragia pulmonar 7%, fuga aérea 5%, hemorragia intraperiventricular de grau III 22%, canal arterial hemodinamicamente significativo 23% e enterocolite necrosante 3%. O grupo que não realizou ventilação invasiva não apresentou hemorragia pulmonar, fuga aérea ou hemorragia intraperiventricular. Dos 65 sobreviventes, 20% desenvolveram displasia broncopulmonar moderada ou grave e 14% retinopatia da prematuridade (≥3/ doença plus). Discussão: O suporte ventilatório dos RNEBP tende a ser progressivamente mais protetor. No grupo analisado, a quase totalidade dos recém-nascidos necessitou de apoio ventilatório, mas cerca de um quarto realizou apenas ventilação não invasiva. A mortalidade global foi elevada, atingindo sobretudo os mais imaturos e em cerca de metade ocorreu no primeiro dia

The Framework “Iberian Massif Landscape and Fluvial Network” in the scope of the Portuguese Geological Heritage Inventory

A diversidade de aspectos do relevo e da drenagem fluvial no Maciço Ibérico justificaram a definição de 5 temas dominantes, agrupados numa categoria temática, com vista ao processo de inventariação de geossítios de valor científico e relevância internacional ou nacional, no âmbito da inventariação do património geológico português em curso. Os temas sucintamente caracterizados são: Macro-geoformas residuais, Geoformas graníticas, Geoformas tectónicas, Sedimentos cenozóicos e Geoformas fluviais. Para cada tema foram definidos alguns subtemas e áreas-chave para a selecção dos geossítios.Five themes were defined taking into account the diversity of geomorphological elements in the Portuguese Iberian Massif. These themes are grouped under a geological framework established to help the selection of geosites with scientific value of national or international significance, under the scope of the ongoing inventory of the Portuguese geological heritage. These themes are: Residual macro-landforms, Granite landforms, Tectonic landforms, Cenozoic sediments, and Fluvial landforms. For each theme, some sub-themes were defined as well as key-areas for the selection of geosites.Este trabalho é apoiado pela Fundação para a Ciência e a Tecnologia, através do financiamento plurianual do CGUP e do projecto de investigação “Identificação, caracterização e conservação do património geológico: uma estratégia de geoconservação para Portugal” (PTDC/CTE-GEX/64966/2006).info:eu-repo/semantics/publishedVersio

Human and murine IFIT1 proteins do not restrict infection of negative-sense RNA viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae families

UNLABELLED: Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5\u27-triphosphates (5\u27-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5\u27-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infected Ifit1(-/-) and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack of Ifit1 gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical between Ifit1(-/-) and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5\u27 ends of IAV gene segments. The affinity for 5\u27-ppp RNA was approximately 10-fold lower than that for non-2\u27-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses. IMPORTANCE: Negative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent history. The host interferon response and induction of antiviral genes contribute to the control of infections by these viruses. IFIT1 is highly induced after virus infection and reportedly has antiviral activity against several RNA and DNA viruses. However, its role in restricting infection by negative-sense RNA viruses remains unclear. In this study, we evaluated the ability of IFIT1 to inhibit negative-sense RNA virus replication and pathogenesis both in vitro and in vivo. Detailed cell culture and animal studies demonstrated that IFIT1 is not a dominant restriction factor against three different families of negative-sense RNA viruses

Transporte mucociliar e sua relação com o nível de atividade física na vida diária em fumadores saudáveis e não fumadores

ResumoObjetivosInvestigar a relação entre o transporte mucociliar e a atividade física na vida diária (AFVD) em fumadores e não fumadores.MétodosCinquenta e dois fumadores foram submetidos à avaliação do transporte mucociliar (Tempo de Trânsito de Sacarina, TTS), dos níveis de monóxido de carbono no ar expirado, da função pulmonar e do histórico tabagístico. Além disso, os sujeitos permaneceram por 6 dias com um pedómetro para determinar o seu nível de AFVD (passos/dia). Os testes também foram realizados em 30 indivíduos não fumadores saudáveis, pareados, que serviram como grupo controlo.ResultadosOs fumadores leves (≤15 cigarros/dia) apresentaram um TTS de 9 (7-11) minutos (mediana [intervalo de confiança]), que foi similar aos não-fumadores (8 [8-11] min; p=0,8). Ambos os fumadores moderados (16-25 cigarros/dia) e severos (>25 cigarros/dia) apresentaram TTS significativamente maior (13 [11-17] min e 13 [10-21] min, respetivamente) do que os não fumadores e fumadores leves (p<0,05 para todos). No grupo de fumadores em geral, não houve correlação estatisticamente significativa entre o TTS e AFVD, índice anos/maço, anos de tabagismo e idade (r<−0,23; p>0,09 para todos). Houve correlação negativa significativa entre o TTS e a AFVD apenas em fumadores leves (r=−0,55; p=0,02) e não fumadores (r=−0,42; p=0,02), mas não em fumadores moderados e pesados.ConclusãoEm fumadores leves e não fumadores, uma melhor função mucociliar está associada a maiores níveis de atividade física diária, ao contrário dos fumadores com função mucociliar diminuída, ou seja, aqueles com consumo moderado e severo de cigarros.AbstractObjectivesTo investigate the relationship between mucociliary transport and physical activity in daily life (PADL) in smokers and nonsmokers.MethodsFifty-two current smokers were submitted to assessment of mucociliary transport (Sacharin Transit Time, STT), carbon monoxide levels in the exhaled air, lung function and smoking history. In addition, subjects kept a pedometer worn at the waist for six days in order to determine their level of PADL (steps/day). The tests were also performed on 30 matched healthy nonsmokers who served as control group.ResultsLight smokers (≤15 cigarettes/day) had a STT of 9 (7-11) min (median [confidence interval]), which was similar to nonsmokers (8 [8-11]min; p=0.8). Both moderate (16-25 cigarettes/day) and heavy (>25 cigarettes/day) smokers had significantly higher STT (13 [11-17] min and 13 [10-21] min, respectively) than nonsmokers and light smokers (p<0.05 for all). There was no difference in the number of steps/day between any of the groups (p>0.05 for all). In the general group of smokers, STT was not significantly correlated with PADL, pack/years index, years of smoking or age (r<−0.23; p>0.09 for all). There was significant negative correlation between STT and PADL only in light smokers (r=−0.55; p=0.02) and nonsmokers (r=−0.42; p=0.02), but not in moderate and heavy smokers.ConclusionIn light smokers and non-smokers, better mucociliary function is associated to higher daily physical activity level, as opposed to the decreased mucociliary function observed in smokers, i.e., those with moderate and heavy cigarette consumption

Integrating distribution kinetics and toxicodynamics to assess repeat dose neurotoxicity in vitro using human BrainSpheres: a case study on amiodarone.

For ethical, economical, and scientific reasons, animal experimentation, used to evaluate the potential neurotoxicity of chemicals before their release in the market, needs to be replaced by new approach methodologies. To illustrate the use of new approach methodologies, the human induced pluripotent stem cell-derived 3D model BrainSpheres was acutely (48 h) or repeatedly (7 days) exposed to amiodarone (0.625-15 µM), a lipophilic antiarrhythmic drug reported to have deleterious effects on the nervous system. Neurotoxicity was assessed using transcriptomics, the immunohistochemistry of cell type-specific markers, and real-time reverse transcription-polymerase chain reaction for various genes involved in the lipid metabolism. By integrating distribution kinetics modeling with neurotoxicity readouts, we show that the observed time- and concentration-dependent increase in the neurotoxic effects of amiodarone is driven by the cellular accumulation of amiodarone after repeated dosing. The development of a compartmental in vitro distribution kinetics model allowed us to predict the change in cell-associated concentrations in BrainSpheres with time and for different exposure scenarios. The results suggest that human cells are intrinsically more sensitive to amiodarone than rodent cells. Amiodarone-induced regulation of lipid metabolism genes was observed in brain cells for the first time. Astrocytes appeared to be the most sensitive human brain cell type in vitro. In conclusion, assessing readouts at different molecular levels after the repeat dosing of human induced pluripotent stem cell-derived BrainSpheres in combination with the compartmental modeling of in vitro kinetics provides a mechanistic means to assess neurotoxicity pathways and refine chemical safety assessment for humans

Evolução cenozóica da área de Longroiva-Vilariça (NE Portugal)

In the Longroiva-Vilariça area, the identification of Cenozoic lithostratigraphic units, the sedimentology and the characterization of its geometric relations with tectonic structures allowed the interpretation of the palaeogeographic main stages: 1) the greenwhitish Vilariça Arkoses (Middle Eocene to Oligocene ?) represent proximal sediments of a very low gradient drainage towards the eastern Spanish Tertiary Duero Basin; 2)Quintãs Formation (late Miocene ?) are brown-reddish coloured piedmont alluvial deposits, correlative of important vertical displacement (western tectonic block relative uplift) along the NNE-SSW indent-linked strike-slip Bragança-Vilariça-Longroiva fault zone, interpreted as a reactivated deep hercynian fracture, with left-lateral movement; 3) the red Sampaio Formation (Gelasian-early Pleistocene ?)was interpreted as downhill conglomeratic deposits related with important overtrusting along this fault zone (the definition of the present-day narrow graben configuration) and correlative of the atlantic hydrographic incision stage beginning; 4) conglomeratic terraces (middle and late Pleistocene ?); 5) alluvial plains and colluvial deposits (Holocene)