Laboratory observations of slow earthquakes and the spectrum of tectonic fault slip modes

Slow earthquakes represent an important conundrum in earthquake physics. While regular earthquakes are catastrophic events with rupture velocities governed by elastic wave speed, the processes that underlie slow fault slip phenomena, including recent discoveries of tremor, slow-slip and low-frequency earthquakes, are less understood. Theoretical models and sparse laboratory observations have provided insights, but the physics of slow fault rupture remain enigmatic. Here we report on laboratory observations that illuminate the mechanics of slow-slip phenomena. We show that a spectrum of slow-slip behaviours arises near the threshold between stable and unstable failure, and is governed by frictional dynamics via the interplay of fault frictional properties, effective normal stress and the elastic stiffness of the surrounding material. This generalizable frictional mechanism may act in concert with other hypothesized processes that damp dynamic ruptures, and is consistent with the broad range of geologic environments where slow earthquakes are observed

The role of fault rock fabric in the dynamics of laboratory faults

Fault stability is inherently linked to the frictional and healing properties of fault rocks and associated fabrics. Their complex interaction controls how the stored elastic energy is dissipated, that is, through creep or seismic motion. In this work, we focus on the relevance of fault fabrics in controlling the reactivation and slip behavior of dolomite-anhydrite analog faults. We designed a set of laboratory experiments where we first develop fault rocks characterized by different grain size reduction and localization at normal stresses of σN = 15, 35, 60, and 100 MPa and second, we reload and reactivate these fault rocks at the frictional stability transition, achieved at σN = 35 MPa by reducing the machine stiffness. If normal stress is lowered this way, reactivation occurs with relatively large stress drops and large peak-slip velocities. Subsequent unstable behavior produces slow stick-slip events with low stress drop and with either asymmetric or Gaussian slip velocity function depending on the inherited fault fabric. If normal stress is raised, deformation is accommodated within angular cataclasites promoting stable slip. The integration of microstructural data (showing brittle reworking of preexisting textures) with mechanical data (documenting restrengthening and dilation upon reactivation) suggests that frictional and chemically assisted healing, which is common in natural faults during the interseismic phase, can be a relevant process in developing large instabilities. We also conclude that fault rock heterogeneity (fault fabric) modulates the slip velocity function and thus the dynamics of repeating stick-slip cycles

Physical and Transport Property Variations Within Carbonate-Bearing Fault Zones: Insights From the Monte Maggio Fault (Central Italy)

AbstractThe physical characterization of carbonate‐bearing normal faults is fundamental for resource development and seismic hazard. Here we report laboratory measurements of density, porosity, Vp, Vs, elastic moduli, and permeability for a range of effective confining pressures (0.1–100 MPa), conducted on samples representing different structural domains of a carbonate‐bearing fault. We find a reduction in porosity from the fault breccia (11.7% total and 6.2% connected) to the main fault plane (9% total and 3.5% connected), with both domains showing higher porosity compared to the protolith (6.8% total and 1.1% connected). With increasing confining pressure, P wave velocity evolves from 4.5 to 5.9 km/s in the fault breccia, is constant at 5.9 km/s approaching the fault plane and is low (4.9 km/s) in clay‐rich fault domains. We find that while the fault breccia shows pressure sensitive behavior (a reduction in permeability from 2 × 10−16 to 2 × 10−17 m2), the cemented cataclasite close to the fault plane is characterized by pressure‐independent behavior (permeability 4 × 10−17 m2). Our results indicate that the deformation processes occurring within the different fault structural domains influence the physical and transport properties of the fault zone. In situ Vp profiles match well the laboratory measurements demonstrating that laboratory data are valuable for implications at larger scale. Combining the experimental values of elastic moduli and frictional properties it results that at shallow crustal levels, M ≤ 1 earthquakes are less favored, in agreement with earthquake‐depth distribution during the L'Aquila 2009 seismic sequence that occurred on carbonates

Early intrathecal infusion of everolimus restores cognitive function and mood in a murine model of Alzheimer's disease

The discovery that mammalian target of rapamycin (mTOR) inhibition increases lifespan in mice and restores/delays many aging phenotypes has led to the identification of a novel potential therapeutic target for the treatment of Alzheimer's disease (AD). Among mTOR inhibitors, everolimus, which has been developed to improve the pharmacokinetic characteristics of rapamycin, has been extensively profiled in preclinical and clinical studies as anticancer and immunosuppressive agent, but no information is available about its potential effects on neurodegenerative disorders. Using a reliable mouse model of AD (3 × Tg-AD mice), we explored whether short-term treatment with everolimus injected directly into the brain by osmotic pumps was able to modify AD-like pathology with low impact on peripheral organs. We first established in non-transgenic mice the stability of everolimus at 37 °C in comparison with rapamycin and, then, evaluated its pharmacokinetics and pharmacodynamics profiles through either a single peripheral (i.p.) or central (i.c.v.) route of administration. Finally, 6-month-old (symptomatic phase) 3 × Tg-AD mice were treated with continuous infusion of either vehicle or everolimus (0.167 μg/μl/day, i.c.v.) using the osmotic pumps. Four weeks after the beginning of infusion, we tested our hypothesis following an integrated approach, including behavioral (tests for cognitive and depressive-like alterations), biochemical and immunohistochemical analyses. Everolimus (i) showed higher stability than rapamycin at 37 °C, (ii) poorly crossed the blood-brain barrier after i.p. injection, (iii) was slowly metabolized in the brain due to a longer t 1/2 in the brain compared to blood, and (iv) was more effective in the CNS when administered centrally compared to a peripheral route. Moreover, the everolimus-induced mTOR inhibition reduced human APP/Aβ and human tau levels and improved cognitive function and depressive-like phenotype in the 3 × Tg-AD mice. The intrathecal infusion of everolimus may be effective to treat early stages of AD-pathology through a short and cyclic administration regimen, with short-term outcomes and a low impact on peripheral organs

On the nature of the galactic early-B hypergiants

Despite their importance to a number of astrophysical fields, the lifecycles of very massive stars are still poorly defined. In order to address this shortcoming, we present a detailed quantitative study of the physical properties of four early-B hypergiants (BHGs); Cyg OB2 #12, zeta Sco, HD190603 and BP Cru. These are combined with an analysis of their long-term spectroscopic and photometric behaviour in order to determine their evolutionary status. The long-term datasets revealed that they are remarkably stable over long periods (>40yr), with the possible exception of zeta Sco prior to the 20th century, in contrast to the typical excursions that characterise luminous blue variables (LBVs). Zeta Sco, HD190603 and BP Cru possess physical properties intermediate between B supergiants and LBVs; we therefore suggest that BHGs are the immediate descendants and progenitors (respectively) of such stars (for initial masses in the range ~30-60Msun). In contrast, while the wind properties of Cyg OB2 #12 are consistent with this hypothesis, the combination of extreme luminosity and spectroscopic mass (~110Msun) and comparatively low temperature means it cannot be accommodated in such a scheme. Likewise, despite its co-location with several LBVs above the Humphreys-Davidson (HD) limit, the lack of long term variability and its unevolved chemistry apparently excludes such an identification. Since such massive stars are not expected to evolve to such cool temperatures, the properties of Cyg OB2 #12 are difficult to understand under current evolutionary paradigms. [ABRIDGED]Comment: 36 pages, 19 figures (of which 17 pages are online supplemental material). Accepted for publication in Astronomy and Astrophysic

Functional Protein Network Activation Mapping Reveals New Potential Molecular Drug Targets for Poor Prognosis Pediatric BCP-ALL

Background: In spite of leukemia therapy improvements obtained over the last decades, therapy is not yet effective in all cases. Current approaches in Acute Lymphoblastic Leukemia (ALL) research focus on identifying new molecular targets to improve outcome for patients with a dismal prognosis. In this light phosphoproteomics seems to hold great promise for the identification of proteins suitable for targeted therapy. Methodology/Principal Findings: We employed Reverse Phase Protein Microarrays to identify aberrantly activated proteins in 118 pediatric B-cell precursor (BCP)-ALL patients. Signal transduction pathways were assayed for activation/expression status of 92 key signalling proteins. We observed an increased activation/expression of several pathways involved in cell proliferation in poor clinical prognosis patients. MLL-rearranged tumours revealed BCL-2 hyperphosphorylation through AMPK activation, which indicates that AMPK could provide a functional role in inhibiting apoptosis in MLL-rearranged patients, and could be considered as a new potential therapeutic target. Second, in patients with poor clinical response to prednisone we observed the up-modulation of LCK activity with respect to patients with good response. This tyrosine-kinase can be down-modulated with clinically used inhibitors, thus modulating LCK activity could be considered for further studies as a new additional therapy for prednisone-resistant patients. Further we also found an association between high levels of CYCLIN E and relapse incidence. Moreover, CYCLIN E is more expressed in early relapsed patients, who usually show an unfavourable prognosis. Conclusions/Significance: We conclude that functional protein pathway activation mapping revealed specific deranged signalling networks in BCP-ALL that could be potentially modulated to produce a better clinical outcome for patients resistant to standard-of-care therapies

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

T-REX OU4 HIRES: the high resolution spectrograph for the E-ELT

The goal of this unit was to consolidate the project for the construction of the high resolution spectrometer of the E-ELT (HIRES). The task included the development of scientific cases and tools to predict the instrumental performances. From the technical point of view it included several R&D activities in collaboration with highly specialized Italian companies; it culminated with the detailed design of a highly modular instrument based on well established technologies. From the management point of view it lead to the consolidation of a large international consortium that spans over 12 countries and includes most of the European and ESO-related institutes interested in high resolution spectroscopy. This consortium is led by INAF; its formal creation is awaiting the official call by ESO for the phase-A study for the HIRES instrument of the E-ELT

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l’Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems