FN-EDA domain knock-in and knock-out mice, as a model for the study of the hepatic fibronectin (FN) functions

Fibronectin (FN) is a multidomain glycoprotein found in plasma and tissue extracellular matrices (ECM). Plasma FN (pFN) is produced and secreted into the bloodstream by the liver. Liver ECM-FN and pFN are characte,rized by the absence of the EDA domain, one of the three FN exons undergoing alternative splicing. However, in pathological situations such as wound healing, the liver produces and accumulates huge amounts of EDA+FN in sinusoidal ECM. In order to study the functions of the FN isoforms produced by the liver, we used two mouse strains devoid of EDA-exon alternative splicing, which constitutively include (EDA+/+ strain) or exclude (EDA-/- strain) the EDA domain. The EDA+/+ strain is characterized by an important decrease of FN levels both in plasma and tissues. Here, we show that the atypycal presence of the EDA domain in hepatocytes affects pFN secretion into the bloodstream and we demonstrate that a high proportion of tissue ECM-FN is supplied by plasma. In fact, removal of the EDA exon only from the liver, by hepatocyt'-specific deletion of the EDA exon, restores normal levels of FN in both plasma and tissues of the EDA+/+ animals. This finding not only suggests that plasma behaves as a sort of FN reservoir for tissue maintenance but also shows for the first time that the pFN contribution to the ECM of tissues is roughly equal to that produced locally. The EDA-/- strain was used to study the role of the EDA domain in the onset of liver fibrosis. In two different liver fibrosis models, we observed that EDA-/- animals develop attenuated fibrosis in comparison to control mice. The important role of the EDA domain in the activation and proliferation of the hepatic stellate cells (HSCs), these are the key cells responsible for the ECM protein overproduction in the fibrotic processes, is demonstrated for the first time in vivo. EDA-/- livers treated to induce fibrosis, present a striking reduction in the number of myofibroblasts or activated HSCs, suggesting that the EDA domain could be a potential target for the treatment of liver fibrosis

Inbound open innovation and firm performance

A number of studies focus on the effects of open innovation on firm performance. However, in our view, previous contributions suffer from two main limitations: at first, there is still no homogeneity in the proposition of what "firm performance" is, according to extant literature. In addition, we see a heterogeneity of implications for the relationship between openness and performance, since there is still no consensus among authors on whether the relationship between openness and firm performance is positive, negative or non-linear.We address this issue through an empirical analysis of a cross-national unbalanced panel data of European firms listed in the five major European markets in the years 2008–2013. We seek to sort the impact of the level of inbound openness, derived by the amount invested in internal development versus the external acquisition of intangible assets on firm performance according to three dimensions: economic performance, measured as the amount of firm turnover; firm financial performance, measured with shares value; and human resources performance, measured as the level of employment.Results of panel data regression show that the effects of both internal development and external acquisition are positive and significant across different dimensions, but their output varies in terms in magnitude and distribution both variables are positively and significantly correlated with firm turnover, and that their effect on the latter is almost equal. In addition, we find that only internal development is positively and significantly correlated with the other two dimensions of performance, once we control for firm-specific time trends. Once we control for relative size of firms in the sample, we see that the effect of openness is more spread out across different class sizes, while the effect of internal development of intangibles influences the economic performance only for larger firms, and increases employment only for relatively smaller firms, while it has no effect on the financial side of performance. Resumen: Una serie de estudios centrados en los efectos de la innovación abierta en el desempeño de la empresa. Sin embargo, en nuestra opinión, las contribuciones anteriores sufren sobretodo de dos limitaciones principales: en principio, todavía, no tenemos ninguna homogeneidad en lo que podemos definir como "desempeño de la empresa" basándonos en los escritos existentes. Además, notamos una heterogeneidad de conceptos y opiniones distintas sobre la relación entre apertura y rendimiento, ya que todavía no hay ningún consenso entre los autores sobre si la relación entre la apertura y el desempeño de la empresa pueda ser algo positivo, negativo o discontinuo.Vamos así profundizando este tema a través de un análisis empírico basado en la comparación de los datos de las empresas europeas que figuran en los cinco principales mercados europeos en los años 2008-2013. Intentamos así de clasificar el impacto del nivel de apertura entrante, derivado del monto invertido para el desarrollo interno -por un lado- y la adquisición externa de bienes intangibles en el rendimiento de la empresa -en el otro- de acuerdo con tres dimensiones: Desempeño económico, medido como la cantidad de rotación de la empresa; desempeño financiero de la empresa, medido con el valor de las acciones; desempeño de los recursos humanos, medido como el nivel de empleo.Los resultados de la elaboración de los datos de nuestro panel muestran que los efectos tanto del desarrollo interno como de la adquisición externa son positivos y significativos en varias y distintas dimensiones, pero su producción puede variar en términos de cantidad y distribución. Ambas las variables se correlacionan positivamente y significativamente en cuanto a la rotación de la empresa y su efecto sobre el último es casi lo mismo. Además, encontramos que solo el desarrollo interno se correlaciona positivamente y significativamente con las otras dos dimensiones del desempeño de la empresa una vez que controlamos las tendencias de tiempo específicas de la empresa misma. Una vez que controlamos el tamaño relativo de las empresas consideradas, nos damos cuenta que el efecto de la apertura está más extendido en diferentes tamaños de clase, mientras que el efecto del desarrollo interno de intangibles influye en el rendimiento económico solo para las empresas más grandes y aumenta el empleo solo para las empresas relativamente más pequeñas; mientras que no tiene ningún efecto en el lado financiero de ningún tipo empresa. JEL classification: O320, O390, Códigos JEL: O320, O390, Keywords: Open innovation, Outside-in, Inbound, Performance, Palabras clave: Innovación abierta, "Afuera/Adentro", Entrante, Rendimient

Time Response of Water-based Liquid Scintillator from X-ray Excitation

Water-based liquid scintillators (WbLS) present an attractive target medium for large-scale detectors with the ability to enhance the separation of Cherenkov and scintillation signals from a single target. This work characterizes the scintillation properties of WbLS samples based on LAB/PPO liquid scintillator (LS). X-ray luminescence spectra, decay profiles, and relative light yields are measured for WbLS of varying LS concentration as well as for pure LS with a range of PPO concentrations up to 90 g/L. The scintillation properties of the WbLS are related to the precursor LAB/PPO: starting from 90 g/L PPO in LAB before synthesis, the resulting WbLS have spectroscopic properties that instead match 10 g/L PPO in LAB. This could indicate that the concentration of active PPO in the WbLS samples depends on their processing.Comment: 6 pages, 7 figures, 2 tables. Submitted to Materials Advances, a journal of the Royal Society of Chemistr

Laboratory and on-site tests for rapid runway repair

The attention to rapid pavement repair has grown fast in recent decades: this topic is strategic for the airport management process for civil purposes and peacekeeping missions. This work presents the results of laboratory and on-site tests for rapid runway repair, in order to analyse and compare technical and mechanical performances of 12 different materials currently used in airport. The study focuses on site repairs, a technique adopted most frequently than repairs with modular elements. After describing mechanical and physical properties of the examined materials (2 bituminous emulsions, 5 cement mortars, 4 cold bituminous mixtures and 1 expanding resin), the study presents the results of carried out mechanical tests. The results demonstrate that the best performing material is a one-component fast setting and hardening cement mortar with graded aggregates. This material allows the runway reopening 6 h after the work. A cold bituminous mixture (bicomponent premixed cold asphalt with water as catalyst) and the ordinary cement concrete allow the reopening to traffic after 18 h, but both ensure a lower service life (1000 coverages) than the cement mortar (10,000 coverages). The obtained results include important information both laboratory level and field, and they could be used by airport management bodies and road agencies when scheduling and evaluating pavement repairs

Multidimensional mobile mapping and integrated approach for the digitalisation of underground transport infrastructure

The tunnel industry has started focusing on the maintenance and management challenges of an existing infrastructure. It is an urgent matter in industrialised countries, where the stakeholders’ attention is increasing at a fast pace considering the incidents and the disruptions caused by improper monitoring and maintenance. This paper presents an innovative methodology to survey and inspect existing railway tunnels through multi-dimensional mobile mapping systems. The proposed approach belongs to the digital strategies for infrastructure maintenance. An integrated multidimensional survey system (ARCHITA) allows for collecting information necessary for the diagnostics of a structure with non-destructive tests. Linear cameras, thermographic cameras, and ground-penetrating radars acquire data to be digitalised and manipulated in different IT environments. The results, in terms of the collected data on structural defects, allow for a new approach for the Management and Identification of the Risk for Existing Tunnels (MIRET). The innovative approach aims at a smart integration of information and models for the Facility Management of the transport system. The workflow for the digitalisation and diagnosis from mobile mapping data has been implemented on two 40km-long metro tunnels

Advanced interpretation of land subsidence by validating multi-interferometric SAR data: the case study of the Anthemountas basin (Northern Greece)

The potential of repeat-pass space borne SAR (Synthetic Aperture Radar) interferometry has been exploited to investigate spatial patterns of land subsidence in the Anthemountas basin, in the northern part of Greece. The PSI (Persistent Scatterer Interferometry) approach, based on the processing of long series of SAR acquisitions, has been applied to forty-two images acquired in 1995–2001 by ERS1/2 satellites. Interferometric results have been analysed at a basin scale as support for land motion mapping and at a local scale for the characterisation of ground motion events affecting the village of Perea in the Thermaikos municipality and the "Macedonia" international airport. PSI results revealed a moderate subsidence phenomenon along the wider coastal zone of Anthemountas basin corresponding to intense groundwater extraction. Highest values, exceeding −20 mm yr−1, were measured in the airport area where the thickest sequence of compressible Quaternary sediments occurs. Intense subsidence has been detected also in the Perea village (maximum deformation of −10 to −15 mm yr−1), where a series of fractures, causing damages to both buildings and infrastructure, occurred in 2005–2006

High Throughput T Epitope Mapping and Vaccine Development

Mapping of antigenic peptide sequences from proteins of relevant pathogens recognized by T helper (Th) and by cytolytic T lymphocytes (CTL) is crucial for vaccine development. In fact, mapping of T-cell epitopes provides useful information for the design of peptide-based vaccines and of peptide libraries to monitor specific cellular immunity in protected individuals, patients and vaccinees. Nevertheless, epitope mapping is a challenging task. In fact, large panels of overlapping peptides need to be tested with lymphocytes to identify the sequences that induce a T-cell response. Since numerous peptide panels from antigenic proteins are to be screened, lymphocytes available from human subjects are a limiting factor. To overcome this limitation, high throughput (HTP) approaches based on miniaturization and automation of T-cell assays are needed. Here we consider the most recent applications of the HTP approach to T epitope mapping. The alternative or complementary use of in silico prediction and experimental epitope definition is discussed in the context of the recent literature. The currently used methods are described with special reference to the possibility of applying the HTP concept to make epitope mapping an easier procedure in terms of time, workload, reagents, cells and overall cost

Multi-Temporal Evaluation of Landslide Movements and Impacts on Buildings in San Fratello (Italy) By Means of C-Band and X-Band PSI Data

This work provides a multi-temporal and spatial investigation of landslide effects in the San Fratello area (Messina province within the Sicily region, Italy), by means of C-band and X-band Persistent Scatterer Interferometry (PSI) data, integrated with in situ field checks and a crack pattern survey. The Sicily region is extensively affected by hydrogeological hazards since several landslides regularly involved local areas across time. In particular, intense and catastrophic landslide phenomena have recently occurred in the San Fratello area; the last event took place in February 2010, causing large economic damage. Thus, the need for an accurate ground motions and impacts mapping and monitoring turns out to be significantly effective, in order to better identify active unstable areas and to help proper risk-mitigation measures planning. The combined use of historical and recent C-band satellites and current X-band Synthetic Aperture Radar sensors of a new generation permits spatially and temporally detection of landslide-induced motions on a local scale and to properly provide a complete multi-temporal evaluation of their effects on the area of interest. PSI ground motion rates are cross-compared with local failures and damage of involved buildings, recently recognized by in situ observations. As a result, the analysis of landslide-induced movements over almost 20 years and the validation of radar data with manufactured crack patterns, permits one to finally achieve a complete and reliable assessment in the San Fratello test site

Updated landslide inventory of the area between the Furiano and Rosmarino creeks (Sicily, Italy)

A 1:10,000 scale landslide inventory map has been prepared for the area between the Furiano and Rosmarino creeks, in the Nebrodi Mountains (north-eastern Sicily, Italy), a territory highly prone to slope failures, due to the local geological and geomorphological settings and intense rainfall. The landslide inventory database included within the Hydrogeological Setting Plan of the Sicily Region has been used as a starting point for this work. The updated inventory map has been compiled through a combination of conventional approaches (i.e. aerial photo-interpretation and field surveys) and new remote sensing techniques (ground deformation measurements obtained by interferometric analysis of satellite Synthetic Aperture Radar images). The new landslide inventory consists of 566 events, classified according to their typology and state of activity

Interacting dark energy from the joint analysis of the power spectrum and bispectrum multipoles with the EFTofLSS

Interacting dark energy models have been suggested as alternatives to the standard cosmological model, $\Lambda$CDM. We focus on a phenomenologically interesting class of dark scattering models that is characterised by pure momentum exchange between dark energy and dark matter. This model extends the parameter space with respect to $\Lambda$CDM by two parameters, $w$ and $A$, which define the dark energy equation of state and the strength of the coupling between dark energy and dark matter, respectively. In order to test non-standard cosmologies with Stage-IV galaxy clustering surveys, it is crucial to model mildly nonlinear scales and perform precision vs accuracy tests. We use the Effective Field Theory of Large-Scale Structure, and we perform validation tests by means of an MCMC analysis using a large set of N-body simulations. We find that adding the bispectrum monopole to the power spectrum multipoles improves the constraints on the dark energy parameters by $\sim 30 \%$ for $k_{\mathrm{max}, B}^{l=0} = 0.11$ $h$ Mpc$^{-1}$ without introducing biases in the parameter estimation. We also find that the same improvement can be achieved with more moderate scale cuts and the use of bias relations, or with the addition of the bispectrum quadrupole. Finally, we study degeneracies between the dark energy parameters and the scalar amplitude $A_\mathrm{s}$ and discuss the corresponding projection effects, as well as degeneracies with other cosmological parameters.Comment: 22 pages, 13 figures; V2: Matches version accepted for publication in MNRAS, includes a new analysis of degeneracies with cosmological parameter