94 research outputs found

    Characterising strongly normalising intuitionistic terms

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    This paper gives a characterisation, via intersection types, of the strongly normalising proof-terms of an intuitionistic sequent calculus (where LJ easily embeds). The soundness of the typing system is reduced to that of a well known typing system with intersection types for the ordinary lambdal-calculus. The completeness of the typing system is obtained from subject expansion at root position. Next we use our result to analyze the characterisation of strong normalisability for three classes of intuitionistic terms: ordinary lambda-terms, LambdaJ-terms (lambda-terms with generalised application), and lambdax-terms (lambda-terms with explicit substitution). We explain via our system why the type systems iin the natural deduction format for LambdaJ and lambdax known from the literature contain extra, exceptional rules for typing generalised application or substitution; and we show a new characterisation of the beta-strongly normalising l-terms, as a corollary to a PSN-result, relating the lambda-calculus and the intuitionistic sequent calculus. Finally, we obtain variants of our characterisation by restricting the set of assignable types to sub-classes of intersection types, notably strict types. In addition, the known characterisation of the beta-strongly normalising lambda-terms in terms of assignment of strict types follows as an easy corollary of our results.Fundação para a Ciência e Tecnologi

    Resource control and intersection types: an intrinsic connection

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    In this paper we investigate the λ\lambda -calculus, a λ\lambda-calculus enriched with resource control. Explicit control of resources is enabled by the presence of erasure and duplication operators, which correspond to thinning and con-traction rules in the type assignment system. We introduce directly the class of λ\lambda -terms and we provide a new treatment of substitution by its decompo-sition into atomic steps. We propose an intersection type assignment system for λ\lambda -calculus which makes a clear correspondence between three roles of variables and three kinds of intersection types. Finally, we provide the characterisation of strong normalisation in λ\lambda -calculus by means of an in-tersection type assignment system. This process uses typeability of normal forms, redex subject expansion and reducibility method.Comment: arXiv admin note: substantial text overlap with arXiv:1306.228

    L-selectin regulates human neutrophil transendothelial migration

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    The migration of circulating neutrophils towards damage/infected tissue is absolutely critical to the inflammatory response. L-selectin is a cell adhesion molecule abundantly expressed on circulating neutrophils. For over two decades, neutrophil L-selectin has been assigned the exclusive role of supporting tethering and rolling - the initial stages of the multi-step adhesion cascade. Here, we provide direct evidence for L-selectin contributing to neutrophil transendothelial migration (TEM). We show that L-selectin co-clusters with PECAM-1 - a well-characterised cell adhesion molecule involved in regulating neutrophil TEM. This co-clustering behaviour occurs specifically during TEM, which serves to augment ectodomain shedding of L-selectin and expedite the time taken for TEM (TTT) to complete. Blocking PECAM-1 signalling (through mutation of its cytoplasmic tail), PECAM-1-dependent adhesion, or L-selectin shedding, led to a significant delay in the TTT. Finally, we show that co-clustering of L-selectin with PECAM-1 occurs specifically across TNF-α- but not IL-1β-activated endothelial monolayers - implying unique adhesion interactomes forming in a cytokine-specific manner. To our knowledge, this is the first report to implicate a non-canonical role for L-selectin in regulating neutrophil TEM

    Serine Phosphorylation of L-Selectin Regulates ERM Binding, Clustering, and Monocyte Protrusion in Transendothelial Migration

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    The migration of circulating leukocytes toward damaged tissue is absolutely fundamental to the inflammatory response, and transendothelial migration (TEM) describes the first cellular barrier that is breached in this process. Human CD14(+) inflammatory monocytes express L-selectin, bestowing a non-canonical role in invasion during TEM. In vivo evidence supports a role for L-selectin in regulating TEM and chemotaxis, but the intracellular mechanism is poorly understood. The ezrin-radixin-moesin (ERM) proteins anchor transmembrane proteins to the cortical actin-based cytoskeleton and additionally act as signaling adaptors. During TEM, the L-selectin tail within transmigrating pseudopods interacts first with ezrin to transduce signals for protrusion, followed by moesin to drive ectodomain shedding of L-selectin to limit protrusion. Collectively, interaction of L-selectin with ezrin and moesin fine-tunes monocyte protrusive behavior in TEM. Using FLIM/FRET approaches, we show that ERM binding is absolutely required for outside-in L-selectin clustering. The cytoplasmic tail of human L-selectin contains two serine (S) residues at positions 364 and 367, and here we show that they play divergent roles in regulating ERM binding. Phospho-S364 blocks direct interaction with ERM, whereas molecular modeling suggests phospho-S367 likely drives desorption of the L-selectin tail from the inner leaflet of the plasma membrane to potentiate ERM binding. Serine-to-alanine mutagenesis of S367, but not S364, significantly reduced monocyte protrusive behavior in TEM under flow conditions. Our data propose a model whereby L-selectin tail desorption from the inner leaflet of the plasma membrane and ERM binding are two separable steps that collectively regulate protrusive behavior in TEM

    A case report: isolation of alysiella filiformis from pig"s lungs

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    Alysiella filiformis is considered a common resident in the oral cavities of many animals. All reports of Alysiella indicate that it is restricted to the oral cavity of warm-blooded vertebrates, where it apparently is nonpathogenic. However, increased losses of young pigs occured in one farm in Serbia. Spumous content in bronchia and partly clotted blood in blood vesels o f the lungs were present. Characteristic signs of oedema disease were present and E. coli serogroup 0139 was isolated. Furthermore, Alysiella filiformis was the single agent isolated from the lungs of diseased pigs. This is the first isolation of Alysiella filiformis from pig lungs

    Fatigue in laser shock peened open-hole thin aluminium specimens

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    An experimental study was performed in order to determine the influence of the sequence of operations on the effectiveness of Laser Shock Peening (LSP) treatment in increasing the fatigue performances of open-hole aluminium specimens. Residual stress measurements, fractographic analysis and FEM analysis were performed, indicating the presence of compressive residual stresses on the surface of the treated specimens and tensile residual stresses in the mid-section along the thickness of the specimens. Negative effects on fatigue lives were encountered on the specimens with the hole already present, while positive effect were observed in specimens in which the hole was drilled after LSP treatment. These results indicate that LSP can be a good solution for “in production” application, in which open holes are to be drilled after the LSP treatment. The application in which LSP is used “in service” on structures with pre-existing cut-outs, has proven to be impracticable in the investigated configuration

    Risks, benefits, and knowledge gaps of non-native tree species in Europe

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    Changing ecosystem conditions and diverse socio-economical events have contributed to an ingrained presence of non-native tree species (NNTs) in the natural and cultural European landscapes. Recent research endeavors have focused on different aspects of NNTs such as legislation, benefits, and risks for forestry, emphasizing that large knowledge gaps remain. As an attempt to fulfill part of these gaps, within the PEN-CAFoRR COST Action (CA19128) network, we established an open-access questionnaire that allows both academic experts and practitioners to provide information regarding NNTs from 20 European countries. Then, we integrated the data originating from the questionnaire, related to the country-based assessment of both peer-reviewed and grey literature, with information from available datasets (EUFORGEN and EU-Forest), which gave the main structure to the study and led to a mixed approach review. Finally, our study provided important insights into the current state of knowledge regarding NNTs. In particular, we highlighted NNTs that have shown to be less commonly addressed in research, raising caution about those characterized by an invasive behavior and used for specific purposes (e.g., wood production, soil recultivation, afforestation, and reforestation). NNTs were especially explored in the context of resilient and adaptive forest management. Moreover, we emphasized the assisted and natural northward migration of NNTs as another underscored pressing issue, which needs to be addressed by joint efforts, especially in the context of the hybridization potential. This study represents an additional effort toward the knowledge enhancement of the NNTs situation in Europe, aiming for a continuously active common source deriving from interprofessional collaboration. Copyright © 2022 Dimitrova, Csilléry, Klisz, Lévesque, Heinrichs, Cailleret, Andivia, Madsen, Böhenius, Cvjetkovic, De Cuyper, de Dato, Ferus, Heinze, Ivetić, Köbölkuti, Lazarević, Lazdina, Maaten, Makovskis, Milovanović, Monteiro, Nonić, Place, Puchalka and Montagnoli

    Endothelial NADPH oxidase-2 promotes interstitial cardiac fibrosis and diastolic dysfunction through proinflammatory effects and endothelial-mesenchymal transition

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    OBJECTIVES: This study sought to investigate the effect of endothelial dysfunction on the development of cardiac hypertrophy and fibrosis. BACKGROUND: Endothelial dysfunction accompanies cardiac hypertrophy and fibrosis, but its contribution to these conditions is unclear. Increased nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2) activation causes endothelial dysfunction. METHODS: Transgenic mice with endothelial-specific NOX2 overexpression (TG mice) and wild-type littermates received long-term angiotensin II (AngII) infusion (1.1 mg/kg/day, 2 weeks) to induce hypertrophy and fibrosis. RESULTS: TG mice had systolic hypertension and hypertrophy similar to those seen in wild-type mice but developed greater cardiac fibrosis and evidence of isolated left ventricular diastolic dysfunction (p < 0.05). TG myocardium had more inflammatory cells and VCAM-1-positive vessels than did wild-type myocardium after AngII treatment (both p < 0.05). TG microvascular endothelial cells (ECs) treated with AngII recruited 2-fold more leukocytes than did wild-type ECs in an in vitro adhesion assay (p < 0.05). However, inflammatory cell NOX2 per se was not essential for the profibrotic effects of AngII. TG showed a higher level of endothelial-mesenchymal transition (EMT) than did wild-type mice after AngII infusion. In cultured ECs treated with AngII, NOX2 enhanced EMT as assessed by the relative expression of fibroblast versus endothelial-specific markers. CONCLUSIONS: AngII-induced endothelial NOX2 activation has profound profibrotic effects in the heart in vivo that lead to a diastolic dysfunction phenotype. Endothelial NOX2 enhances EMT and has proinflammatory effects. This may be an important mechanism underlying cardiac fibrosis and diastolic dysfunction during increased renin-angiotensin activation

    The Effect of Sequence of Operations on Fatigue Life of LSP Treated Open-hole Aluminium Specimens

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    Fastener holes in aeronautical structures are typical sources of fatigue cracks due to their induced local stress concentration. A very efficient solution to this problem is to establish compressive residual stresses around the fastener holes that retard the fatigue crack nucleation and its subsequent local propagation. Previous work done on the subject of the application of LSP treatment on thin, open-hole specimens [1] has proven that the LSP effect on fatigue life of treated specimens can be detrimental, if the process is not properly optimized. In fact, it was shown that the capability of the LSP to introduce compressive residual stresses around fastener holes in thin-walled structures representative of typical aircraft constructions was not superior to the performance of conventional techniques, such as cold-working
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