The 3D numerical simulation of near-source ground motion during the Marsica earthquake, central Italy, 100 years later

In this paper we show 3D physics-based numerical simulations of ground motion during one of the most devastating earthquakes in the recent Italian history, occurred on Jan 13, 1915, Marsica, Central Italy. The results provide a realistic estimate of the earthquake ground motion and fit reasonably well both the geodetic measurements of permanent ground settlement, and the observed macroseismic distribution of damage. In addition, these results provide a very useful benchmark to improve the current knowledge of near-source earthquake ground motion, including evaluation of the best distance metrics to describe the spatial variability of the peak values of ground motion, the relative importance of fault normal vs fault parallel components, the conditions under which vertical ground motion may prevail, as well as the adequacy of 1D vs 3D modelling of site amplification effects

Critical issues in the determination of the bentonite cation exchange capacity

The swelling pressure and transport properties of bentonites are controlled by the electric charge density of solid particles, which is commonly estimated from the laboratory measurement of the cation exchange capacity (CEC). However, the standard ammonium displacement method for CEC determination does not take into account the fabric changes that occur in bentonites under exposure to high salt concentration solutions. A series of laboratory tests was conducted to assess the relevance of such a critical issue, by varying the concentration of the extracting KCl solution with respect to that of the standard test. The obtained results show that the release of the adsorbed ammonium cations depends on the bentonite fabric, which is controlled by the KCl concentration. As a consequence, the ammonium displacement method may provide an unrepresentative estimate of the CEC of bentonites. The methylene blue titration method, despite its apparently more limited accuracy, instead seems to provide a more reliable estimation of the CEC, as the bentonite fabric is maintained dispersed during the test

Correction to: Implementation and Assessment Methodologies of Teachers' Training Courses for STEM Activities

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Implementation and Assessment Methodologies of Teachers' Training Courses for STEM Activities

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Motives to use Facebook and problematic Facebook use in adolescents

Background and aims There is a growing body of evidence suggesting that problematic Facebook use (PFU) is an emerging problem, particularly among adolescents. Although a number of motivations explaining why people engage in frequent Facebook use have been identified, less is known about the specific psychological needs underlying PFU. The aim of this study is to test a model designed to assess the unique contribution of psychological motives for using Facebook to the different PFU dimensions in a sample of adolescents. Methods A total of 864 Italian adolescents participated in the study. Multivariate multiple regression was run to test whether the four motives were differently associated with problematic dimensions. Results The results showed that the two motives with negative valence (coping and conformity) were significantly linked to the five dimensions of PFU, whereas the two motives with positive valence (enhancement and social) appeared to be weaker predictors for three out of these five dimensions. Discussion and conclusion In conclusion, psychological motives for using Facebook appeared to significantly contribute to explaining PFU among adolescents, and should be considered by researchers and educational practitioners

Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

The duality of macrophage function in Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia and, in some patients, is accompanied by resistance to both chemotherapeutics and immunotherapeutics. In this review we will discuss the role of tumour associated macrophages (TAMs) in promoting CLL cell survival and resistance to immunotherapeutics. In addition, we will discuss mechanisms by which TAMs suppress T-cell mediated antitumour responses. Thus, targeting macrophages could be used to i) reduce the leukaemic burden via the induction of T-cell-mediated antitumour responses, ii) to reduce pro-survival signalling and enhance response to conventional chemotherapeutics or iii) enhance the response to therapeutic antibodies in current clinical use

Genome-wide protein QTL mapping identifies human plasma kallikrein as a post-translational regulator of serum uPAR levels

The soluble cleaved urokinase plasminogen activator receptor (scuPAR) is a circulating protein detected in multiple diseases, including various cancers, cardiovascular disease, and kidney disease, where elevated levels of scuPAR have been associated with worsening prognosis and increased disease aggressiveness. We aimed to identify novel genetic and biomolecular mechanisms regulating scuPAR levels. Elevated serum scuPAR levels were identified in asthma (n=514) and chronic obstructive pulmonary disease (COPD; n=219) cohorts when compared to controls (n=96). In these cohorts, a genome-wide association study of serum scuPAR levels identified a human plasma kallikrein gene (KLKB1) promoter polymorphism (rs4253238) associated with serum scuPAR levels in a control/asthma population (P=1.17×10−7), which was also observed in a COPD population (combined P=5.04×10−12). Using a fluorescent assay, we demonstrated that serum KLKB1 enzymatic activity was driven by rs4253238 and is inverse to scuPAR levels. Biochemical analysis identified that KLKB1 cleaves scuPAR and negates scuPAR's effects on primary human bronchial epithelial cells (HBECs) in vitro. Chymotrypsin was used as a proproteolytic control, while basal HBECs were used as a control to define scuPAR-driven effects. In summary, we reveal a novel post-translational regulatory mechanism for scuPAR using a hypothesis-free approach with implications for multiple human diseases