Cognitive dynamics of norm compliance. From norm adoption to flexible automated conformity

In this paper, an integrated, cognitive view of different mechanisms, reasons and pathways to norm compliance is presented. After a short introduction, theories of norm compliance are reviewed, and found to group in four main typologies: the rational choice model of norm compliance; theories based on conditional preferences to conformity, theories of thoughtless conformity, and theories of norm internalization. In the third section of the paper, the normative architecture EMIL-A is presented. Previous work discussed the epistemic module of this normative architecture, allowing for the generation of normative beliefs being formed. The fourth and fifth sections present the pragmatic modules of EMIL-A, i.e. norm adoption??leading to normative goals??and norm compliance??leading to their execution. Not only are several alternative reasons for norm adoption shown, but also several pathways to norm compliance are identified. Finally, a summary and ideas for future works conclude the paper.     

Preparation of 4-inch Ir/YSZ/Si(001) substrates for the large-area deposition of single-crystal diamond

Diamond/Ir/YSZ/Si(001) is currently the most promising multilayer structure for the future realisation of large-area diamond single crystals. A decisive key is the preparation of the iridium layers on silicon. It is shown in this work that high quality iridium films with mosaic spread below 0.2° can be grown on oxide buffer layers with a mosaic spread higher than 1°. An averaging process during the coalescence of the iridium islands provides a plausible mechanism for this phenomenon. The oxide buffer and the iridium overlayers can be grown homogeneously on 4-inch wafers in a similar quality as for 1 × 1 cm² samples. Bias enhanced nucleation followed by 40 h growth on the large-area Ir/YSZ/Si(001) wafers yields diamond films with a mosaicity of 0.16° (tilt) and 0.34° (twist). For a further increase of the area of heteroepitaxial diamond nucleation the homogeneity of the plasma discharge has to be improved.     

Transmission electron microscopy study of the very early stages of diamond growth on iridium

The diamond nuclei generated during bias enhanced nucleation (BEN) on iridium were not detected so far by high resolution transmission electron microscopy (HRTEM). The aim of the present work was to investigate their earliest appearance after BEN by applying very short growth steps, ranging from 5 s to 1 min. On all the samples with growth step crystalline diamond could be identified unequivocally by HRTEM and reflection high energy electron diffraction (RHEED). After 5 s the former nuclei have evolved into crystallites of 2 nm thickness and about 10 nm width. At that time the carbon precursor phase which appears amorphous in HRTEM and which was formed by the ion bombardment has largely disappeared. After 10 s no residues are left, which proves that the 1–2 nm-thick amorphous carbon layer is only stable under biasing conditions. The rapid etching of the precursor phase and the simultaneous slow increase in volume of the tiny diamond crystals results in a minimum in carbon coverage several seconds after termination of the BEN process.     

Identification of Potential Leukocyte Biomarkers Related to Drug Recovery of CFTR: Clinical Applications in Cystic Fibrosis

The aim of this study was the identification of specific proteomic profiles, related to a restored cystic fibrosis transmembrane conductance regulator (CFTR) activity in cystic fibrosis (CF) leukocytes before and after ex vivo treatment with the potentiator VX770. We used leukocytes, isolated from CF patients carrying residual function mutations and eligible for Ivacaftor therapy, and performed CFTR activity together with proteomic analyses through micro-LC–MS. Bioinformatic analyses of the results obtained revealed the downregulation of proteins belonging to the leukocyte transendothelial migration and regulation of actin cytoskeleton pathways when CFTR activity was rescued by VX770 treatment. In particular, we focused our attention on matrix metalloproteinase 9 (MMP9), because the high expression of this protease potentially contributes to parenchyma lung destruction and dysfunction in CF. Thus, the downregulation of MMP9 could represent one of the possible positive effects of VX770 in decreasing the disease progression, and a potential biomarker for the prediction of the efficacy of therapies targeting the defect of Cl⁻ transport in CF.     

Molecular Modeling Studies on the Human Neuropeptide S Receptor and Its Antagonists

Neuropeptide S (NPS) is a 20‐residue peptide of great interest due to its potential involvement in several biological processes such as arousal, anxiety, and food intake. The NPS receptor belongs to the rhodopsin‐like G‐protein‐coupled receptor superfamily, and several polymorphisms and isoforms of this receptor are associated with asthma, allergies, and bronchial hyper‐responsiveness, in particular the Asn 107 Ile mutation. Limited structural information is available for this peptide–receptor system, particularly regarding the NPS receptor structure, its nonpeptide ligands, and the molecular aspects of agonist and antagonist binding processes. In this work, rhodopsin‐based homology models of the NPS receptor and its Asn 107 Ile variant were built and refined in a membrane bilayer model, and binding modes for nonpeptide antagonists were simulated. This study provides the first structural study of the human NPS receptor, and the results provide a starting point for further characterization of the binding modes of its antagonists, and for the rational design of new NPS receptor ligands.     

Results of an integration study of a diagnostics port plug in ITER

Diagnostics in ITER are mandatory to characterize the parameters of plasma and study its interactions with plasma-facing components. Diagnostics components in the vicinity of the plasma are supported by metallic structures called port plugs. At the tokamak mid-plane, these components are installed in port plugs through intermediate structures called drawers. Apart from hosting the diagnostics, the port plugs act as shielding against neutrons and gammas, in order to limit the nuclear loads in crucial components (such as diagnostics and superconducting coils) as well as the dose levels in the controlled zones of the tokamak. The radiation shielding function of the port plugs is ensured through an optimized mixture of heavy metallic materials and water, forming shielding blocks surrounding the diagnostics and called Diagnostic Shield Modules (DSMs). These DSMs constitute the rear part of the drawers (the front part being composed of the Diagnostic First Wall). This paper presents the main results of a study performed in Europe on the integration of a particular diagnostics port plug, the Equatorial Port Plug 1 (EPP1). The paper first provides the results of the EPP1 diagnostics integration analysis. In a second step it focuses on the design of the EPP1 DSMs and summarizes the major results of a thorough set of analyses aiming at studying the DSMs behaviour under different loads, suggesting recommendations to improve their current design.     

Erythrocytes as a Model for Heavy Metal-Related Vascular Dysfunction: The Protective Effect of Dietary Components

Heavy metals are toxic environmental pollutants associated with severe ecological and human health risks. Among them is mercury (Hg), widespread in air, soil, and water, due to its peculiar geo-biochemical cycle. The clinical consequences of Hg exposure include neurotoxicity and nephrotoxicity. Furthermore, increased risk for cardiovascular diseases is also reported due to a direct effect on cardiovascular tissues, including endothelial cells, recently identified as important targets for the harmful action of heavy metals. In this review, we will discuss the rationale for the potential use of erythrocytes as a surrogate model to study Hg-related toxicity on the cardiovascular system. The toxic effects of Hg on erythrocytes have been amply investigated in the last few years. Among the observed alterations, phosphatidylserine exposure has been proposed as an underlying mechanism responsible for Hg-induced increased proatherogenic and prothrombotic activity of these cells. Furthermore, following Hg-exposure, a decrease in NOS activity has also been reported, with consequent lowering of NO bioavailability, thus impairing endothelial function. An additional mechanism that may induce a decrease in NO availability is the generation of an oxidative microenvironment. Finally, considering that chronic Hg exposure mainly occurs through contaminated foods, the protective effect of dietary components is also discussed.     

Selective Capture of Anti-N-glucosylated NTHi Adhesin Peptide Antibodies by a Multivalent Dextran Conjugate

Tentacle-like polymers decorated with several copies of peptide antigens can be interesting tools for increasing the ability to capture circulating antibodies in patient sera, using cooperative effects for stronger avidity. We previously showed that antibodies from multiple sclerosis (MS) patient sera preferentially recognize hyperglucosylated adhesin protein HMW1ct of non-typeable Haemophilus influenzae (NTHi). We selected the C-terminal HMW1ct(1347–1354) minimal epitope and prepared the diglucosylated analogue Ac-KAN(Glc)VTLN(Glc)TTG-K(N₃)-NH₂ to graft a 40 kDa dextran scaffold modified with glycidyl-propargyl moieties to perform a copper catalyzed alkyne-azide coupling reaction (CuAAC). Quantitative NMR measurements allowed the characterization of the peptide loading (19.5 %) on the multivalent dextran conjugate. This novel polymeric structure displayed optimal capturing properties of both IgG and, more interestingly, IgM antibodies in MS sera. Specific antibodies from a representative MS serum, were successfully depleted using a Sepharose resin bearing the new glucosylated multivalent conjugate, as confirmed by ELISA. These results may offer a promising proof-of-concept for the selective purification of high affinity autoantibodies from sera of autoimmune patients, in general, and of specific high affinity antibodies against a minimally glcosylated epitope Asn(Glc) from sera of multiple sclerosis (MS) patients, in particular.