Labelled Lambda-calculi with Explicit Copy and Erase

We present two rewriting systems that define labelled explicit substitution lambda-calculi. Our work is motivated by the close correspondence between Levy's labelled lambda-calculus and paths in proof-nets, which played an important role in the understanding of the Geometry of Interaction. The structure of the labels in Levy's labelled lambda-calculus relates to the multiplicative information of paths; the novelty of our work is that we design labelled explicit substitution calculi that also keep track of exponential information present in call-by-value and call-by-name translations of the lambda-calculus into linear logic proof-nets

A Fully Labelled Lambda Calculus: Towards Closed Reduction in the Geometry of Interaction Machine

AbstractWe investigate the possibility of performing new reduction strategies with the Geometry of Interaction Machine (GOIm). To this purpose, we appeal to Lévy's labelled lambda calculus whose labels describe: a) the path that the GOIm will follow in the graph of a term and b) the operations that the GOIm requires to compute the multiplicative part from the Multiplicative and Exponential Linear Logic encoding that the machine uses. Our goal is to unveil the missing exponential information in the structure of the labels. This will provide us with a tool to talk about strategies for computing paths with the GOIm

New Developments in Environment Machines

AbstractIn this paper we discuss and compare abstract machines for the lambda-calculus, implementing various evaluation strategies. Starting from the well-known Categorical abstract machine (CAM) and Krivine's abstract machine (KAM), we develop two families of machines that differ in the way they treat environments. The first family is inspired by the work on closed reduction strategies, whereas the second is built in the spirit of the jumping machines based on the work done on Linear Logic

Single dose pharmacodynamics of amphotericin B against Aspergillus species in an in vitro pharmacokinetic/pharmacodynamic model

Conventional MIC testing of amphotericin B results in narrow MIC ranges challenging the detection of resistant strains. In order to discern amphotericin B pharmacodynamics, the in vitro activity of amphotericin B was studied against Aspergillus isolates with the same MIC with a new in vitro pharmacokinetic/pharmacodynamic (PK/PD) model that simulates amphotericin B human plasma levels. Clinical isolates of A. fumigatus, A. terreus and A flavus with the same CLSI modal MICs of 1 mg/l were exposed to amphotericin B concentrations following the plasma concentration-time profile after single bolus administration with Cmax 0.6, 1.2, 2.4 and 4.8 mg/L. Fungal growth was monitored up to 72h based on galactomannan production. Complete growth inhibition was observed only against A. fumigatus with amphotericin B Cmax ≥2.4 mg/L. At lower Cmaxs 0.6 and 1.2 mg/L, a significant growth delay of 34h and 52h was observed, respectively (pA flavus>A. terreus in the in vitro PK/PD model possibly reflecting the different concentration- and time-dependent inhibitory/killing activities amphotericin B exerting against these species

Smoking and Pulmonary Fibrosis: Novel Insights

The relationship between smoking and pulmonary fibrosis is under debate and intense investigation. The aim of this paper is to review the existing literature and identify further areas of research interest. Recently the negative influence of cigarette smoking on IPF outcome was highlighted, as non-smokers exhibit a better survival than ex-smokers and combined current- and ex-smokers. In patients with non-specific interstitial pneumonia (NSIP), a high prevalence of emphysema was recently demonstrated, providing an indirect support for a smoking pathogenetic hypothesis in NSIP. The coexistence of pulmonary fibrosis and emphysema has been extensively described in a syndrome termed combined pulmonary fibrosis and emphysema (CPFE). Connective tissue disorders (CTDs) are a group of autoimmune diseases which affect the lung, as one of the most common and severe manifestations. However, the relationship between smoking and autoimmune disorders is still conflicting. Rheumatoid arthritis results from the interaction between genetic and environmental factors, while the best established environmental factor is tobacco smoking. Smoking has also a negative impact on the response of the RA patients to treatment. The aforementioned smoking-related implications give rise to further research questions and certainly provide one more important reason for physicians to advocate smoking cessation and smoke-free environment

Effects of antifibrotic agents on TGF-β1, CTGF and IFN-γ expression in patients with idiopathic pulmonary fibrosis

SummaryIdiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-γ-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-β, CTGF) and immunomodulatory/antimicrobial activity (IFN-γ), in the lungs of patients with IPF.Fourteen (14) patients with an established diagnosis of IPF received either 200μg of IFN-γ-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor β1 (TGF-β1), connective-tissue growth factor (CTGF), and interferon-γ (IFN-γ) genes in lung tissue before and after treatment with IFN-γ-1b or colchicine.Marked mRNA expression of TGF-β1 and CTGF, but complete lack of interferon-γ was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-γ gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-β1 remained almost stable before and after treatment, in the IFN-γ-1b group, while TGF-β1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-γ-1b group (p=0.04). In addition, the IFN-γ-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02).In conclusion, we report the effect of antifibrotic agents (IFN-γ-1b and colchicine) in TGF-β, CTGF, and endogenous IFN-γ gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings