IL-17A in Human Liver: Significant Source of Inflammation and Trigger of Liver Fibrosis Initiation

IL-17A is considered to guide liver inflammation and fibrosis. From twenty-two human liver samples of different fibrosis stages (F0 to F4), IL-17A, IL-22, and TGFβ1 protein expression in liver tissue lysates were analyzed. Ten paired samples of liver tissue (F0–F1 stage) and blood from the same patient were used to analyze intrahepatic and blood T-lymphoid IL-17A⁺ cells by flow cytometry. The analyses have been performed regardless of pathology, considering the stage of fibrosis. Human liver tissue was used for the primary human liver slice cultures, followed by subsequent cytokine stimulation and fibrotic markers’ analysis by ELISA. IL-17A production in human liver tissue was significantly higher in the early fibrotic stage compared with the advanced stage. Th17 T cells and, to a lesser extent, MAIT cells were the main sources of IL-17A in both compartments, the liver and the blood. Moreover, the presence of liver Th17IL-17A⁺INFγ⁺ cells was detected in the liver. IL-17A stimulation of human liver slice culture increased the expression of profibrotic and pro-inflammatory markers. IL-17A, secreted by Th17 and MAIT cells in the liver, triggered fibrosis by inducing the expression of IL-6 and profibrotic markers and could be a target for antifibrotic treatment. Further amplitude studies are needed to confirm the current results.     

A Novel Homozygous Variant in DYSF Gene Is Associated with Autosomal Recessive Limb Girdle Muscular Dystrophy R2/2B

Mutations in the DYSF gene, encoding dysferlin, are responsible for Limb Girdle Muscular Dystrophy type R2/2B (LGMDR2/2B), Miyoshi myopathy (MM), and Distal Myopathy with Anterior Tibialis onset (MDAT). The size of the gene and the reported inter and intra familial phenotypic variability make early diagnosis difficult. Genetic analysis was conducted using Next Gene Sequencing (NGS), with a panel of 40 Muscular Dystrophies associated genes we designed. In the present study, we report a new missense variant c.5033G>A, p.Cys1678Tyr ({"type":"entrez-nucleotide","attrs":{"text":"NM_003494","term_id":"1675063869"}}NM_003494) in the exon 45 of DYSF gene related to Limb Girdle Muscular Dystrophy type R2/2B in a 57-year-old patient affected with LGMD from a consanguineous family of south Italy. Both healthy parents carried this variant in heterozygosity. Genetic analysis extended to two moderately affected sisters of the proband, showed the presence of the variant c.5033G>A in both in homozygosity. These data indicate a probable pathological role of the variant c.5033G>A never reported before in the onset of LGMDR2/2B, pointing at the NGS as powerful tool for identifying LGMD subtypes. Moreover, the collection and the networking of genetic data will increase power of genetic-molecular investigation, the management of at-risk individuals, the development of new therapeutic targets and a personalized medicine.     

Peer to peer trade in HTM5 meta model for agent oriented cloud robotic systems

Cloud computing is a methodology and not a technology. Adaptation of cloud computing services for robotic applications is relatively straightforward while adaptation of underlying ideas will require a new design attitude. Cloud computing is a cost-effective and dynamic business model. Currently cloud robotics is understood as a client server methodology which enables robots utilize resources and services placed at centralized servers. These cloud servers treat robots as any other client computer offering them platform, infrastructure, process or algorithm as a service. HTM5 is an OMG MDA based multi-view meta-model for agent oriented development of cloud robotic systems. HTM5 encourages design of peer-to-peer service ecosystems based on an open registry and matchmaking mechanism. In peer-to-peer cloud robotics, a robot can trade its hardware, software and functional resources as a service to other robots in the ecosystem. The peer-to-peer trade in such systems may be driven by contracts and relationships between its member agents. This article discusses trade-view model of HTM5 methodology and its use in developing a cloud robotic ecosystem that implements peer-to-peer, contract based economy. The article also presents a case study with experiments that implement distributed artificial intelligence and peer-to-peer service oriented trade on simulated and real robot colonies.     

The Synchronous Approach to Designing Reactive Systems

Synchronous programming is available through several formally defined languages having very different characteristics: Esterel is imperative, while Lustre and Signal are declarative in style; Statecharts and Argos are graphical languages that allow one to program by constructing hierarchical automata. Our motivation for taking the synchronous design paradigm further, integrating imperative, declarative (or dataflow), and graphical programming styles, is that real systems typically have components that match each of these profiles. This paper motivates our interest in the mixed language programming of embedded software around a number of examples, and sketches the semantical foundation of the Synchronie toolset which ensures a coherent computational model. This toolset supports a design trajectory that incorporates rapid prototyping and systematic testing for early design validation, an object oriented development methodology for long term software management, and formal verification at the level of automatically generated object code.     

Investigation of the Fuzzy Complex between RSV Nucleoprotein and Phosphoprotein to Optimize an Inhibition Assay by Fluorescence Polarization

The interaction between Respiratory Syncytial Virus phosphoprotein P and nucleoprotein N is essential for the formation of the holo RSV polymerase that carries out replication. In vitro screening of antivirals targeting the N-P protein interaction requires a molecular interaction model, ideally consisting of a complex between N protein and a short peptide corresponding to the C-terminal tail of the P protein. However, the flexibility of C-terminal P peptides as well as their phosphorylation status play a role in binding and may bias the outcome of an inhibition assay. We therefore investigated binding affinities and dynamics of this interaction by testing two N protein constructs and P peptides of different lengths and composition, using nuclear magnetic resonance and fluorescence polarization (FP). We show that, although the last C-terminal Phe₂₄₁ residue is the main determinant for anchoring P to N, only longer peptides afford sub-micromolar affinity, despite increasing mobility towards the N-terminus. We investigated competitive binding by peptides and small compounds, including molecules used as fluorescent labels in FP. Based on these results, we draw optimized parameters for a robust RSV N-P inhibition assay and validated this assay with the M76 molecule, which displays antiviral properties, for further screening of chemical libraries.     

Mice Lacking Gpr179 with Complete Congenital Stationary Night Blindness Are a Good Model for Myopia

Mutations in GPR179 are one of the most common causes of autosomal recessive complete congenital stationary night blindness (cCSNB). This retinal disease is characterized in patients by impaired dim and night vision, associated with other ocular symptoms, including high myopia. cCSNB is caused by a complete loss of signal transmission from photoreceptors to ON-bipolar cells. In this study, we hypothesized that the lack of Gpr179 and the subsequent impaired ON-pathway could lead to myopic features in a mouse model of cCSNB. Using ultra performance liquid chromatography, we show that adult Gpr179^−/− mice have a significant decrease in both retinal dopamine and 3,4-dihydroxyphenylacetic acid, compared to Gpr179^+/+ mice. This alteration of the dopaminergic system is thought to be correlated with an increased susceptibility to lens-induced myopia but does not affect the natural refractive development. Altogether, our data added a novel myopia model, which could be used to identify therapeutic interventions.     

Thermal and economic evaluation of heat recovery measures for indoor ice rinks

A comparative study of three ventilation systems supplying air to a typical Canadian indoor ice rink illustrates the power, energy and operating cost savings which can be achieved by using the relatively warm air from the air cooled condensers of the refrigeration system. The direct use of this warm air for ventilation results in a reduction of energy consumption during the winter amounting to 24.2% of the yearly consumption of the heating system. On the other hand, the use of a heat exchanger to heat the ventilation air results in energy consumption reductions throughout the year. Depending on the size of the heat exchanger these gains can be as high as 60.8% of the heating energy consumption by the existing system. Based on actual prices of electricity and the heat exchanger it is established that the cost savings over the life of the equipment are at least three times higher than the cost of the heat exchanger.     

Al2O3-ZrO2 Finely Structured Multilayer Architectures from Suspension Plasma Spraying

Suspension plasma spraying (SPS) is an alternative to conventional atmospheric plasma spraying (APS) aiming at manufacturing thinner layers (i.e., 10-100 μm) due to the specific size of the feedstock particles, from a few tens of nanometers to a few micrometers. The staking of lamellae and particles, which present a diameter ranging from 0.1 to 2.0 μm and an average thickness from 20 to 300 nm, permits to manufacture finely structured layers. Moreover, it appears as a versatile process able to manufacture different coating architectures according to the operating parameters (suspension properties, injection configuration, plasma properties, spray distance, torch scan velocity, scanning step, etc.). However, the different parameters controlling the properties of the coating, and their interdependences, are not yet fully identified. Thus, the aim of this paper is, on the one hand, to better understand the influence of operating parameters on the coating manufacturing mechanisms (in particular, the plasma gas mixture effect) and, on the other hand, to produce Al₂O₃-ZrO₂ finely structured layers with large varieties of architectures. For this purpose, a simple theoretical model was used to describe the plasma torch operating conditions at the nozzle exit, based on experimental data (mass enthalpy, arc current intensity, thermophysical properties of plasma forming gases, etc.) and the influences of the spray parameters were determined by mean of the study of sizes and shapes of spray beads. The results enabled then to reach a better understanding of involved phenomena and their interactions on the final coating architectures permitting to manufacture several types of microstructures.