Mapping, Structure and Modulation of PPI

Because of the key relevance of protein–protein interactions (PPI) in diseases, the modulation of protein-protein complexes is of relevant clinical significance. The successful design of binding compounds modulating PPI requires a detailed knowledge of the involved protein-protein system at molecular level, and investigation of the structural motifs that drive the association of the proteins at the recognition interface. These elements represent hot spots of the protein binding free energy, define the complex lifetime and possible modulation strategies. Here, we review the advanced technologies used to map the PPI involved in human diseases, to investigate the structure-function features of protein complexes, and to discover effective ligands that modulate the PPI for therapeutic intervention

Seismic measurements to reveal short-term variations in the elastic properties of the Earth crust

Since the late the late ’60s-early ’70s era seismologists started developed theories that included variations of the elastic property of the Earth crust and the state of stress and its evolution crust prior to the occurrence of a large earthquake. Among the others the theory of the dilatancy (Scholz et al., 1973): when a rock is subject to stress, the rock grains are shifted generating micro-cracks, thus the rock itself increases its volume. Inside the fractured rock, fluid saturation and pore pressure play an important role in earthquake nucleation, by modulating the effective stress. Thus measuring the variations of wave speed and of anisotropic parameter in time can be highly informative on how the stress leading to a major fault failure builds up. In 80s and 90s such kind of research on earthquake precursor slowed down and the priority was given to seismic hazard and ground motions studies, which are very important since these are the basis for the building codes in many countries. Today we have dense and sophisticated seismic networks to measure wave-fields characteristics: we archive continuous waveform data recorded at three components broad-band seismometers, we almost routinely obtain high resolution earthquake locations. Therefore we are ready to start to systematically look at seismic-wave propagation properties to possibly reveal short-term variations in the elastic properties of the Earth crust. One seismological quantity which, since the ‘70s, is recognized to be diagnostic of the level of fracturation and/or of the pore pressure in the rock, hence of its state of stress, is the ratio between the compressional (P-wave) and the shear (S-wave) seismic velocities, the Vp/Vs (Nur, 1972; Kisslinger and Engdahl, 1973). Variations of this ratio have been recently observed and measured during the preparatory phase of a major earthquake (Lucente et al. 2010). In active fault areas and volcanoes, tectonic stress variation influences fracture field orientation and fluid migration processes, whose evolution with time can be monitored through the measurement of the anisotropic pa- rameters (Miller and Savage, 2001; Piccinini et al., 2006). Through the study of S waves anisotropy it is therefore potentially possible to measure the presence, migration and state of the fluid in the rock traveled by seismic waves, thus providing a valuable route to understanding the seismogenic phenomena and their precursors (Crampin & Gao, 2010). In terms of determination of Earth crust elastic properties, recent studies (Brenguier et al., 2008; Chen et al., 2010; Zaccarelli et al., 2011) have shown how it is possible to estimate the relative variations in the wave speed through the analysis of the crosscorrelation of ambient seismic noise. In this paper we analyze in detail two seismological methods dealing with shear wave splitting and seismic noise cross correlation: a short historical review, their theoretical bases, the problems, learnings, limitations and perspec- tives. Moreover we discuss the results of these methods already applied on the data recorded in the L’Aquila region, before and after the destructive earthquake of April 6th 2009, represent their self an interesting case study

Passive seismology and deep structure in central Italy

n the last decade temporary teleseismic transects have become a powerful tool for investigating the crustal and upper mantle structure. In order to gain a clearer picture of the lithosphere-asthenosphere structure in peninsular Italy, between 1994 and 1996, we have deployed three teleseismic transects in northern, central, and southern Apennines, in the framework of the project GeoModAp (European Community contract EV5V-CT94–0464). Some hundreds of teleseisms were recorded at each deployment which lasted between 3 and 4 months. Although many analyses are still in progress, the availability of this high quality data allowed us to refine tomographic images of the lithosphere-asthenosphere structure with an improved resolution in the northern and central Apennines, and to study the deformation of the upper mantle looking at seismic anisotropy through shear-wave splitting analysis. Also, a study of the depth and geometry of the Moho through the receiver function technique is in progress. Tomographic results from the northernmost 1994 and the central 1995 teleseismic experiments confirm that a high-velocity anomaly (HVA) does exist in the upper 200–250 km and is confined to the northern Apenninic arc. This HVA, already interpreted as a fragment of subducted lithosphere is better defined by the new temporary data, compared to previous works, based only on data from permanent stations. No clear high-velocity anomalies are detected in the upper 250 km below the central Apennines, suggesting either a slab window due to a detachment below southern peninsular Italy, or a thinner, perhaps continental slab of Adriatic lithosphere not detectable by standard tomography. We found clear evidence of seismic anisotropy in the uppermost mantle, related to the main tectonic processes which affected the studied regions, either NE–SW compressional deformation of the lithosphere beneath the mountain belt, or arc-parallel asthenospheric flow (both giving NW–SE fast polarization direction), and successive extensional deformation ( E–W trending) in the back-arc basin of northern Tyrrhenian and Tuscany. Preliminary results of receiver function studies in the northern Apennines show that the Moho depth is well defined in the Tyrrhenian and Adriatic regions while its geometry underneath the mountain belt is not yet well constrained, due to the observed high complexity.Published479-4934T. Sismicità dell'ItaliaJCR Journa

Multi-segment rupture of the 2016 Amatrice-Visso-Norcia seismic sequence (central Italy) constrained by the first high-quality catalog of Early Aftershocks

We present the first high-quality catalog of early aftershocks of the three mainshocks of the 2016 central Italy Amatrice-Visso-Norcia normal faulting sequence. We located 10,574 manually picked aftershocks with a robust probabilistic, non-linear method achieving a significant improvement in the solution accuracy and magnitude completeness with respect to previous studies. Aftershock distribution and relocated mainshocks give insight into the complex architecture of major causative and subsidiary faults, thus providing crucial constraints on multi-segment rupture models. We document reactivation and kinematic inversion of a WNW-dipping listric structure, referable to the inherited Mts Sibillini Thrust (MST) that controlled segmentation of the causative normal faults. Spatial partitioning of aftershocks evidences that the MST lateral ramp had a dual control on rupture propagation, behaving as a barrier for the Amatrice and Visso mainshocks, and later as an asperity for the Norcia mainshock. We hypothesize that the Visso mainshock re-activated also the deep part of an optimally oriented preexisting thrust. Aftershock patterns reveal that the Amatrice Mw5.4 aftershock and the Norcia mainshock ruptured two distinct antithetic faults 3-4 km apart. Therefore, our results suggest to consider both the MST cross structure and the subsidiary antithetic fault in the finite-fault source modelling of the Norcia earthquake.Published69214T. Sismicità dell'ItaliaJCR Journa

X-Ray Detected Magnetic Hysteresis of Thermally Evaporated Terbium Double-Decker Oriented Films

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AlpArray-Italy: Site description and noise characterization

Within the framework of the European collaborative research initiative AlpArray (http://www.alparray.ethz. ch), the Istituto Nazionale di Geofisica e Vulcanolgia (INGV) deployed overall 20 broad-band seismic stations in Northern Italy and on two islands in the Tyrrhenian Sea (Capraia and Montecristo) during Fall-Winter 2015. The temporary deployment (16 stations) will run for two to three years and 4 INGV National Seismic Network accelerometric sites are now equipped with additional per- manent broad-band sensors. The 16 temporary stations are equipped with REF TEK 130 digitizers and Nanometrics Trillium Compact 120 s sensors, a couple have Nanometrics Trillium 120P sensors and one a Streckeisen STS2. For each site we describe the settings and discuss the noise levels, the site effects and the preliminary sensitivity analysis.Published39-528T. Sismologia in tempo realeJCR Journa

A first-in-class Wiskott-Aldrich syndrome protein activator with anti-tumor activity in hematologic cancers

Hematological cancers are among the most common cancers in adults and children. Despite significant improvements in therapies, many patients still succumb to the disease. Therefore, novel therapies are needed. The Wiskott-Aldrich syndrome protein (WASp) family regulates actin assembly in conjunction with the Arp2/3 complex, a ubiquitous nucleation factor. WASp is expressed exclusively in hematopoietic cells and exists in two allosteric conformations: autoinhibited or activated. Here, we describe the development of EG-011, a first-in-class small molecule activator of the WASp auto-inhibited form. EG-011 possesses in vitro and in vivo anti-tumor activity as a single agent in lymphoma, leukemia, and multiple myeloma, including models of secondary resistance to PI3K, BTK, and proteasome inhibitors. The in vitro activity was confirmed in a lymphoma xenograft. Actin polymerization and WASp binding was demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs-inducing actin polymerization

Catalogo completo della sequenza sismica di Amatrice-Visso-Norcia (Italia centrale, Bollettino Sismico Italiano 2016-2018)

In questo lavoro presentiamo il catalogo completo delle localizzazioni dei terremoti appartenenti alla più importante sequenza sismica avvenuta in Italia negli ultimi 30 anni, ovvero la sequenza sismica di Amatrice-Visso-Norcia (AVN) iniziata il 24 Agosto del 2016 in Appennino centrale. Si tratta di 102582 eventi sismici registrati dalle 129 stazioni della Rete Sismica Nazionale (RSN, http://doi.org/10.13127/SD/X0FXNH7QFY) e della rete temporanea installata nella regione epicentrale (Moretti et al., 2016), dal 14 agosto 2016 al 31 agosto 2018 e analizzati manualmente dagli analisti del Bollettino Sismico Italiano (BSI, http://cnt.rm.ingv.it/bsi). Le fasi P ed S e le ampiezze di questi terremoti, stimate in tempo reale nella sala di sorveglianza dell’Istituto Nazionale di Geofisica e Vulcanologia (INGV) di Roma, sono state successivamente riviste in dettaglio, per tutti gli eventi di M≽ 2.3, con l’intento di aumentare la qualità dei parametri di localizzazione e della stima della magnitudo. Gli analisti hanno inoltre inserito le fasi P ed S osservate a quelle stazioni che il sistema di acquisizione non aveva eventualmente incluso nelle soluzioni automatiche in real-time. Per i primi mesi della sequenza l'analisi ha riguardato anche l’integrazione delle registrazioni di 9 stazioni temporanee standalone che non entravano automaticamente nelle localizzazioni della sala sismica; per i giorni nei quali si sono verificati gli eventi di M≽ 5.5 la revisione è stata particolarmente accurata anche per eventi di magnitudo inferiore a 2.3 (Improta et al. 2019) Il dataset così costruito consiste in 25496 terremoti rivisti dagli analisti del bollettino (versione 1000) e 77426 eventi elaborati dai turnisti in sala sismica (versione 100). Le 1705987 fasi P che ne sono derivate, e le 1271757 fasi S, sono disponibili nel database ISIDe (DOI: 10.13127/ISIDe). Tutte le letture dei tempi di arrivo sono state utilizzate per localizzare gli ipocentri della sequenza utilizzando il codice di inversione non lineare NonLinLoc (NLL, Lomax et al., 2001): l’utilizzo di questa tecnica ha migliorato, rispetto ai lavori precedenti, la stima dei parametri ipocentrali fornendo delle soluzioni più robuste ai fini della ricostruzione sismotettonica dell’area interessata dalla sequenza sismica AVN. Rispetto ai dati forniti in tempo reale dal personale in servizio di sorveglianza sismica dell’INGV, questo nuovo catalogo presenta un notevole miglioramento in termini di omogeneità della stima della ML, almeno nel range definito dalla soglia inferiore di revisione pari a ML≽ 2.3. Questa maggiore omogeneità del catalogo permetterà ulteriori analisi per la stima della Mc (Magnitudo di completezza). Inoltre, all’interno del catalogo sono presenti 75 terremoti con ML≽4.0: per 47 di questi eventi sismici abbiamo calcolato il meccanismo focale a partire dalle prime polarità utilizzando il codice FPFIT (Reasenberg and Oppenheimer, 1985). Un catalogo di questo tipo, di alta qualità, basato quindi su un imponente numero di fasi e ampiezze riviste manualmente, ha una particolare importanza e può essere un valido riferimento per l’applicazione per esempio di tecniche di detection basate sulla crosscorrelazione di registrazioni di terremoti templates, per la validazione di cataloghi composti da letture automatiche dei tempi di arrivo, o anche per l’ottimizzazione di algoritmi di picking automatici. La qualità delle localizzazioni dei mainshocks e degli aftershocks della sequenza sismica AVN diventa fondamentale per capire l'analisi dell'evoluzione spazio-temporale della sismicità, anche di bassa magnitudo, e le complesse geometrie delle faglie attivate durante la sequenza sismica, contestualmente alle relazioni tra esse esistenti.PublishedRoma - Italia4IT. Banche dat

The Italian Earthquakes and Tsunami Monitoring and Surveillance Systems

The Osservatorio Nazionale Terremoti (ONT) is the Italian seismic operational centre for monitoring earthquake, it is part of Istituto Nazionale di Geofisica e Vulcanologia (INGV) the largest Italian research institution, with focus in Earth Sciences. INGV runs the Italian National Seismic Network (network code IV) and other networks at national scale for monitoring earthquakes and tsunami. INGV is a primary node of European Integrated Data Archive (EIDA) for archiving and distributing, continuous, quality checked seismic waveforms (strong motion and weak motion recordings). ONT designed the data acquisition system to accomplish, in near-real-time, automatic earthquake detection, hypocentre and magnitude determination and evaluation of moment tensors, shake maps and other products. Database archiving of all parametric results are closely linked to the existing procedures of the INGV seismic monitoring environment and surveillance procedures. ONT organize the Italian earthquake surveillance service and the tsunami alert service (INGV is Tsunami Service Provider of the ICG/NEAM for the entire Mediterranean basin). We provide information to the Dipartimento di Protezione Civile (DPC) and to several Mediterranean countries. Earthquakes information are revised routinely by the analysts of the Italian Seismic Bulletin. The results are published on the web and are available to the scientific community and the general public.PublishedMontreal1SR TERREMOTI - Sorveglianza Sismica e Allerta Tsunam