Applying the damage assessment for rapid response approach to the august 24 M6 event of the seismic sequence in central Italy (2016)

Seismic monitoring networks are increasingly being used in urban areas to record and locate earthquakes. Recordings in the proximity of buildings also allow assessing, as a first approximation, the expected building damage. The DARR (Damage Assessment for Rapid Response) method provides local-scale information on expected damage patterns. The potential of this approach is discussed here for the August 24 M6 event of the Central Italy seismic sequence (2016-2017). We focus only on the first event of the sequence because cumulative damage is outside the scope of this study. The earthquake recordings are available from two Italian monitoring networks: the Italian Accelerometric Archive (ITACA) and the OSS (Osservatorio Sismico delle Strutture), which collects data from monitored buildings and bridges in Italy. We selected four target areas (Amatrice, Norcia, Visso and Sulmona) characterized by different epicentral distances and building typologies, that suffered different levels of damage during the M6 event on 24 August 2016. Using recordings either in the free field or in the basement of buildings, the expected relative displacement of building typologies common in the studied areas is calculated with the DARR method. Using predefined damage thresholds from literature, the obtained results allow quantifying the expected damage for dominant building typologies in the surroundings of the recording sites. We investigate and discuss the potential use and applicability of the DARR method in different areas depending on the epicentral distance and building characteristics. The results indicate that the DARR approach is useful for supporting and improving rapid response activities after a seismic event

What information could the main actors of liquid biopsy provide? A representative case of non-small cell lung cancer (NSCLC)

In non-small cell lung cancer (NSCLC), there is a consensus regarding the use of liquid biopsy, generally, to detect "druggable" mutations and, in particular, to monitor tyrosine kinase inhibitor (TKI) treatments. However, whether circulating tumor cells (CTCs) are better tools than cell-free DNA (cfDNA), is still a matter of debate, mainly concerning which antigen(s) we should use to investigating simultaneously both epithelial and epithelial-to-mesenchymal transient (EMT) phenotype in the same sample of CTCs. To address this item, we exploited here a single-tube liquid biopsy, to detect both epithelial cell adhesion molecule (EpCAM)-positive CTCs and EpCAM-low/negative CTCs, because down-modulation of EpCAM is considered the first step in EMT. Furthermore, we analyzed the DNA from CTCs of four different phenotypes (ctcDNA), according to their EpCAM expression and cytokeratin pattern, and circulating tumor DNA (ctDNA) by droplet digital PCR (ddPCR), in order to disclose activating and resistancedriving mutations. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution

A multi-scale risk assessment for tephra fallout and airborne concentration from multiple Icelandic volcanoes – Part 1: Hazard assessment

This is the final version of the article. Available from EGU via the DOI in this record.In order to assist the elaboration of proactive measures for the management of future volcanic eruptions in Iceland, we developed a new scenario-based approach to assess the hazard associated with tephra dispersal and sedimentation at various scales and for multiple sources. The target volcanoes are Hekla, Katla, Eyjafjallajökull and Askja, selected either for their high probabilities of eruption and/or their high potential impact. By coupling tephrostratigraphic studies, probabilistic techniques and modelling, we developed comprehensive eruption scenarios for both short- and long-lasting eruptions and compiled hazard maps for tephra ground deposition at a national scale and air concentration at a European scale using the TEPHRA2 and FALL3D models, respectively. New algorithms for the identification of realistic sets of eruptive source parameters are investigated, which assist the generation of probability density functions of eruption source parameters for the selected scenarios. Aggregation processes were accounted for using various empirical models. Outcomes, i.e. probabilities conditioned to the occurrence of an eruption, help the assessment and comparison of hazard levels at different scales. For example, at a national scale Askja has a 5–10% probability of blanketing the easternmost half of the country with a tephra accumulation of at least 1 kg m−2. At a continental scale, Katla has a 5–10% probability of producing ash clouds with concentrations of 2 mg m−3 over the UK, Scandinavia and northern Europe with a mean arrival time of 48–72 h and a mean persistence time of 6–18 h. In a companion paper, Scaini et al. (2014) present a vulnerability assessment for Iceland to ground deposition of tephra and for the European air traffic to airborne ash which, combined with the outcomes of the present paper, constitute one of the first comprehensive multi-scale risk assessment associated with tephra dispersal and sedimentation.S. Biass is supported by SNF (#200021-129997) and ESF/MemoVolc (#5193) subsides. C. Scaini is partly supported by the Spanish Research Project ATMOST (CGL2009-10244) and by the SNF (IZK0Z2_ 142343)

A multi-scale risk assessment for tephra fallout and airborne concentration from multiple Icelandic volcanoes – Part 2: Vulnerability and impact

This is the final version of the article. Available from EGU via the DOI in this record.We perform a multi-scale impact assessment of tephra fallout and dispersal from explosive volcanic activity in Iceland. A companion paper (Biass et al., 2014; "A multi-scale risk assessment of tephra fallout and airborne concentration from multiple Icelandic volcanoes – Part I: hazard assessment") introduces a multi-scale probabilistic assessment of tephra hazard based on selected eruptive scenarios at four Icelandic volcanoes (Hekla, Askja, Eyjafjallajökull and Katla) and presents probabilistic hazard maps for tephra accumulation in Iceland and tephra dispersal across Europe. Here, we present the associated vulnerability and impact assessment that describes the importance of single features at national and European levels and considers several vulnerability indicators for tephra dispersal and deposition. At the national scale, we focus on physical, systemic and economic vulnerability of Iceland to tephra fallout, whereas at the European scale we focus on the systemic vulnerability of the air traffic system to tephra dispersal. This is the first vulnerability and impact assessment analysis of this type and, although it does not include all the aspects of physical and systemic vulnerability, it allows for identifying areas on which further specific analysis should be performed. Results include vulnerability maps for Iceland and European airspace and allow for the qualitative identification of the impacts at both scales in the case of an eruption occurring. Maps produced at the national scale show that tephra accumulation associated with all eruptive scenarios considered can disrupt the main electricity network, in particular in relation to an eruption of Askja. Results also show that several power plants would be affected if an eruption occurred at Hekla, Askja or Katla, causing a substantial systemic impact due to their importance for the Icelandic economy. Moreover, the Askja and Katla eruptive scenarios considered could have substantial impacts on agricultural activities (crops and pastures). At the European scale, eruptive scenarios at Askja and Katla are likely to affect European airspace, having substantial impacts, in particular, in the Keflavík and London flight information regions (FIRs), but also at FIRs above France, Germany and Scandinavia. Impacts would be particularly intense in the case of long-lasting activity at Katla. The occurrence of eruptive scenarios at Hekla is likely to produce high impacts at Keflavík FIR and London FIRs, and, in the case of higher magnitude, can also impact France's FIRs. Results could support land use and emergency planning at the national level and risk management strategies of the European air traffic system. Although we focus on Iceland, the proposed methodology could be applied to other active volcanic areas, enhancing the long-term tephra risk management. Moreover, the outcomes of this work pose the basis for quantitative analyses of expected impacts and their integration in a multi-risk framework.This work has been funded by the Spanish research project “Atmospheric transport models and massive parallelism: applications to volcanic ash clouds and dispersion of pollutants at an urban micro-scale” (ATMOST, CGL2009-10244) and the Fonds National Suisse project “Volcanic-Ash Dispersal from Selected Icelandic Volcanoes: Risk Assessment for the European Region” (IZK0Z2_142343). S. Biass is supported by SNF (#200021-129997) and ESF/MemoVolc (#5193) subsidies

Towards specific T–H relationships: FRIBAS database for better characterization of RC and URM buildings

FRIBAS database is an open access database composed of the characteristics of 312 buildings (71 masonry, 237 reinforced concrete and 4 mixed types). It collects and harmonizes data from different surveys performed on buildings in the Basilicata and Friuli Venezia Giulia regions (Southern and Northeastern Italy, respectively). Each building is defined by 37 parameters related to the building and foundation soil characteristics. The building and soil fundamental periods were experimentally estimated based on ambient noise measurements. FRIBAS gave us the opportunity to study the influence of the main characteristics of buildings and the soil-building interaction effect to their structural response. In this study, we have used the FRIBAS dataset to investigate how the building period varies as a function of construction materials and soil types. Our results motivate the need of going beyond a 'one-fits-all' numerical period-height (T-H) relationship for generic building typologies provided by seismic codes, towards specific T-H relationships that account for both soil and building typologies

Short-term angiotensin II treatment regulates cardiac nanomechanics via microtubule modifications.

Mechanical properties of single myocytes contribute to the whole heart performance, but the measurement of mechanics in living cells at high resolution with minimal force interaction remains challenging. Angiotensin II (AngII) is a peptide hormone that regulates a number of physiological functions, including heart performance. It has also been shown to contribute to cell mechanics by inducing cell stiffening. Using non-contact high-resolution Scanning Ion Conductance Microscopy (SICM), we determine simultaneously cell topography and membrane transverse Young's modulus (YM) by a constant pressure application through a nanopipette. While applying pressure, the vertical position is recorded and a deformation map is generated from which YM can be calculated and corrected for the uneven geometry. High resolution of this method also allows studying specific membrane subdomains, such as Z-grooves and crests. We found that short-term AngII treatment reduces the transversal YM in isolated adult rat cardiomyocytes acting via an AT1 receptor. Blocking either a TGF-β1 receptor or Rho kinase abolishes this effect. Analysis of the cytoskeleton showed that AngII depletes microtubules by decreasing long-lived detyrosinated and acetylated microtubule populations. Interestingly, in the failing cardiomyocytes, which are stiffer than controls, the short-term AngII treatment also reduces the YM, thus normalizing the mechanical state of cells. This suggests that the short-term softening effect of AngII on cardiac cells is opposite to the well-characterized long-term hypertrophic effect. In conclusion, we generate a precise nanoscale indication map of location-specific transverse cortical YM within the cell and this can substantially advance our understanding of cellular mechanics in a physiological environment, for example in isolated cardiac myocytes

Short-term angiotensin II treatment regulates cardiac nanomechanics: Via microtubule modifications

Mechanical properties of single myocytes contribute to the whole heart performance, but the measurement of mechanics in living cells at high resolution with minimal force interaction remains challenging. Angiotensin II (AngII) is a peptide hormone that regulates a number of physiological functions, including heart performance. It has also been shown to contribute to cell mechanics by inducing cell stiffening. Using non-contact high-resolution Scanning Ion Conductance Microscopy (SICM), we determine simultaneously cell topography and membrane transverse Young's modulus (YM) by a constant pressure application through a nanopipette. While applying pressure, the vertical position is recorded and a deformation map is generated from which YM can be calculated and corrected for the uneven geometry. High resolution of this method also allows studying specific membrane subdomains, such as Z-grooves and crests. We found that short-term AngII treatment reduces the transversal YM in isolated adult rat cardiomyocytes acting via an AT1 receptor. Blocking either a TGF-β1 receptor or Rho kinase abolishes this effect. Analysis of the cytoskeleton showed that AngII depletes microtubules by decreasing long-lived detyrosinated and acetylated microtubule populations. Interestingly, in the failing cardiomyocytes, which are stiffer than controls, the short-term AngII treatment also reduces the YM, thus normalizing the mechanical state of cells. This suggests that the short-term softening effect of AngII on cardiac cells is opposite to the well-characterized long-term hypertrophic effect. In conclusion, we generate a precise nanoscale indication map of location-specific transverse cortical YM within the cell and this can substantially advance our understanding of cellular mechanics in a physiological environment, for example in isolated cardiac myocytes

Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene

A large body of evidence strongly suggests that the p53 tumor suppressor pathway is central in reducing cancer frequency in vertebrates. The protein product of the haploinsufficient mouse double minute 2 (MDM2) oncogene binds to and inhibits the p53 protein. Recent studies of human genetic variants in p53 and MDM2 have shown that single nucleotide polymorphisms (SNPs) can affect p53 signaling, confer cancer risk, and suggest that the pathway is under evolutionary selective pressure (1–4). In this report, we analyze the haplotype structure of MDM4, a structural homolog of MDM2, in several different human populations. Unusual patterns of linkage disequilibrium (LD) in the haplotype distribution of MDM4 indicate the presence of candidate SNPs that may also modify the efficacy of the p53 pathway. Association studies in 5 different patient populations reveal that these SNPs in MDM4 confer an increased risk for, or early onset of, human breast and ovarian cancers in Ashkenazi Jewish and European cohorts, respectively. This report not only implicates MDM4 as a key regulator of tumorigenesis in the human breast and ovary, but also exploits for the first time evolutionary driven linkage disequilibrium as a means to select SNPs of p53 pathway genes that might be clinically relevant