Molecular Biomarkers in Idiopathic Pulmonary Fibrosis: State of the Art and Future Directions

Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.     

The canonical processes of a dramatized approach to information presentation

This paper describes the application “Carletto the spider” in terms of the mapping with the canonical processes of media production. “Carletto the spider” is a character-based guide to a historical site and implements the Dramatour approach for the design of drama-based interactive presentations. Dramatization makes presentations more engaging, thus improving the reception of the content by the user. The major technical issue of the approach is the segmentation of the presentation into audiovisual units that are edited on-the-fly in a way that guarantees dramatic continuity while adapting to the user response. We describe the workflow of the application and its mapping to the canonical processes of media production, envisaging possible standardizations for the application portability.     

Assessing landscape preferences: a visual choice experiment in the agricultural region of Märkische Schweiz,Germany

Natural amenities and the aesthetic value of agricultural landscapes are important territorial assets for improving rural tourism and the quality of the living environment. To identify which characteristics shape the visual quality of a landscape, a stated-preference survey was conducted (N = 200) using photorealistic landscape visualisations of four different landscape attributes (point green elements, linear green elements, crop diversity and presence of livestock). We estimated respondents’ preferences for landscape attributes, examined the extent of agreement among respondents and identified socio-economic factors influencing their responses. Results revealed that point elements had the highest general preference. About 70% of respondents preferred diverse and highly structured landscapes, while about 30% of respondents had opposing preferences. Preferences were also found to be dependent on the individual’s sociocultural background, such as their level of education, gender or age. These results can help to improve the multi-objective targeting of policies by including an aesthetic value perspective.     

Small‐b and Fixed‐b Asymptotics for Weighted Covariance Estimation in Fractional Cointegration

In a standard cointegrating framework, Phillips (1991) introduced the weighted covariance (WC) estimator of cointegrating parameters. Later, Marinucci (2000) applied this estimator to fractional circumstances and, like Phillips (1991), analysed the so‐called small‐b asymptotic approximation to its sampling distribution. Recently, an alternative limiting theory (fixed‐b asymptotics) has been successfully employed to approximate sampling distributions. With the purpose of comparing both approaches, we derive here the fixed‐b limit of WC estimators in a fractional setting, filling also some gaps in the traditional (small‐b) theory. We also provide some Monte Carlo evidence that suggests that the fixed‐b limit is more accurate.     

Optical micro-structures fabricated on top of optical fibers by means of two-photon photopolymerization

In this work we report, for the first time to our knowledge, the possibility to fabricate various structures, with good optical proprieties, on the top of optical fibers, using the two-photon lithography (TPL) technique. We show the convenience of this approach to quickly create generic 3D shapes using a single set-up by contrast to past shape-dependent methods. A set of different structures are fabricated and characterized to demonstrate the versatility of this approach and their high optical quality.     

Modeling and biological investigations of an unusual behavior of novel synthesized acridine-based polyamine ligands in the binding of double helix and G-quadruplex DNA

Three novel 2,7-substituted acridine derivatives were designed and synthesized to investigate the effect of this functionalization on their interaction with double-stranded and G-quadruplex DNA. Detailed investigations of their ability to bind both forms of DNA were carried out by using spectrophotometric, electrophoretic, and computational approaches. The ligands in this study are characterized by an open-chain (L1) or a macrocyclic (L2, L3) framework. The aliphatic amine groups in the macrocycles are joined by ethylene (L2) or propylene chains (L3). L1 behaved similarly to the lead compound m-AMSA, efficiently intercalating into dsDNA, but stabilizing G-quadruplex structures poorly, probably due to the modest stabilization effect exerted by its protonated polyamine chains. L2 and L3, containing small polyamine macrocyclic frameworks, are known to adopt a rather bent and rigid conformation; thus they are generally expected to be sterically impeded from recognizing dsDNA according to an intercalative binding mode. This was confirmed to be true for L3. Nevertheless, we show that L2 can give rise to efficient π-π and H-bonding interactions with dsDNA. Additionally, stacking interactions allowed L2 to stabilize the G-quadruplex structure: using the human telomeric sequence, we observed the preferential induction of tetrameric G-quadruplex forms. Thus, the presence of short ethylene spacers seems to be essential for obtaining a correct match between the binding sites of L2 and the nucleobases on both DNA forms investigated. Furthermore, current modeling methodologies, including docking and MD simulations and free energy calculations, provide structural evidence of an interaction mode for L2 that is different from that of L3; this could explain the unusual stabilizing ability of the ligands (L2>L3>L1) toward G-quadruplex that was observed in this study.     

Measurement of ultimate tensile strength and Young modulus in LYSO scintillating crystals

Scintillating crystals are employed in high energy physics, in medical imaging, diagnostic and security. Two mechanical properties of lutetium-yttrium oxyorthosilicate cerium-doped Lu_2(1−x)Y_2xSiO₅:Ce with x=0.1 (LYSO) crystals have been measured: the ultimate tensile stress (σ_UTS) and the Young elastic modulus (E). Measurements are made by means of a 4-points loading device and the experimental results account for an elastic-brittle stress-strain relation, which depends heavily on the specimen preparation and the material defects. σ_UTS along the [0 1 0] tensile direction ranges within 68.14 and 115.61 MPa, which, in the lowest case, is more than twice with respect to those measured for PbWO₄ (PWO), exhibiting a marked difference between the annealed and the not-annealed samples. The mean elastic modulus (E), along the same direction, is E=1.80×10¹¹ (±2.15×10¹⁰) N/m², with lower dispersion respect to UTS data. This type of analysis and study can be included into quality control procedures of crystals, based on samples taken out of production; such procedures can be established for industrial processing of crystals aimed to the high energy physics (calorimeters) and medical imaging (PET, etc.) applications.     

Wetting and interfacial phenomena in relation to joining of alumina via Co/Nb/Co interlayers

When designing multilayer metallic interlayers for transient-liquid-phase (TLP) bonding of ceramics, the phenomena that occur at the interface between the liquid metal alloy formed at the joining temperature and the solid ceramic to be joined have a major effect on the success or failure of the joining process. To assess the behavior of liquids that could develop when using Co/Nb/Co trilayers to bond Al₂O₃ ceramics, the wettability and interfacial behavior of pure Co and Co–Nb alloys on sapphire and polycrystalline Al₂O₃ were studied. Contact angles were measured at 1500 °C using the sessile-drop technique, and the microstructures of the resulting metal/ceramic interfaces were characterized by scanning electron microscopy and energy-dispersive spectroscopy. Observations were assessed and evaluated in the context of predictions of thermodynamic properties. Additions of Nb to Co reduced the contact angle and thus improved the adhesion between the ceramic and metal. Nb additions also enhanced dissolution of Al₂O₃.     

Integrating load balancing and locality in the parallelization of irregular problems

An irregular problem models the evolution of a system where several elements are irregularly distributed in a domain. The evolution modifies this distribution in a way that cannot be foreseen and the behavior of each element depends upon the elements close to it according to a problem dependent relation. Starting from a hierarchical representation of the domain, we define a parallelization methodology that includes a load balancing strategy that preserves this locality property and a strategy to collect information distributed onto the processing nodes.