Platelet activation in type 2 diabetes mellitus

The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, prothrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population. © 2004 International Society on Thrombosis and Haemostasis

Shake table testing of a tuned mass damper inerter (Tmdi)-equipped structure and nonlinear dynamic modeling under harmonic excitations

This paper presents preliminary experimental results from a novel shaking table testing campaign investigating the dynamic response of a two-degree-of-freedom (2DOF) physical specimen with a grounded inerter under harmonic base excitation and contributes a nonlinear dynamic model capturing the behavior of the test specimen. The latter consists of a primary mass connected to the ground through a high damping rubber isolator (HDRI) and a secondary mass connected to the primary mass through a second HDRI. Further, a flywheel-based rack-and-pinion inerter prototype device is used to connect the secondary mass to the ground. The resulting specimen resembles the tuned mass damper inerter (TMDI) configuration with grounded inerter analytically defined and numerically assessed by the authors in a number of previous publications. Physical specimens with three different inerter coefficients are tested on the shake table under sine-sweep excitation with three different amplitudes. Experimental frequency response functions (FRFs) are derived manifesting a softening nonlinear behavior of the specimens and enhanced vibration suppression with increased inerter coefficient. Further, a 2DOF parametric nonlinear model of the specimen is established accounting for non-ideal inerter device behavior and its potential to characterize experimental response time-histories, FRFs, and force-displacement relationships of the HDRIs and of the inerter is verified

Late Holocene landscape change history related to the Alpine Fault determined from drowned forests in Lake Poerua, Westland, New Zealand

Abstract. Lake Poerua is a small, shallow lake that abuts the scarp of the Alpine Fault on the West Coast of New Zealand's South Island. Radiocarbon dates from drowned podocarp trees on the lake floor, a sediment core from a rangefront alluvial fan, and living tree ring ages have been used to deduce the late Holocene history of the lake. Remnant drowned stumps of kahikatea (Dacrycarpus dacrydioides) at 1.7–1.9 m water depth yield a preferred time-of-death age at 1766–1807 AD, while a dryland podocarp and kahikatea stumps at 2.4–2.6 m yield preferred time-of-death ages of ca. 1459–1626 AD. These age ranges are matched to, but offset from, the timings of Alpine Fault rupture events at ca. 1717 AD, and either ca. 1615 or 1430 AD. Alluvial fan detritus dated from a core into the toe of a rangefront alluvial fan, at an equivalent depth to the maximum depth of the modern lake (6.7 m), yields a calibrated age of AD 1223–1413. This age is similar to the timing of an earlier Alpine Fault rupture event at ca. 1230 AD ± 50 yr. Kahikatea trees growing on rangefront fans give ages of up to 270 yr, which is consistent with alluvial fan aggradation following the 1717 AD earthquake. The elevation levels of the lake and fan imply a causal and chronological link between lake-level rise and Alpine Fault rupture. The results of this study suggest that the growth of large, coalescing alluvial fans (Dry and Evans Creek fans) originating from landslides within the rangefront of the Alpine Fault and the rise in the level of Lake Poerua may occur within a decade or so of large Alpine Fault earthquakes that rupture adjacent to this area. These rises have in turn drowned lowland forests that fringed the lake. Radiocarbon chronologies built using OxCal show that a series of massive landscape changes beginning with fault rupture, followed by landsliding, fan sedimentation and lake expansion. However, drowned Kahikatea trees may be poor candidates for intimately dating these events, as they may be able to tolerate water for several decades after metre-scale lake level rises have occurred

WP8 Modelling of topographic signal: Detailed characterisation of individual structures

This deliverable will describe in detail results obtained during the project for four key areas of the Po Plain, the target area for the INGV contribution to the project. The four area are: 1) Coastal Marche region (southeastern Po Plain – see Section 1) 2) Mantova/Mincio River area (central Po Plain – see Section 2) 3) Mirandola/Secchia-Panaro Rivers area (southern-central Po Plain – see Section 3) 4) Soncino/Oglio River area (western Po Plain – see Section 4

Identification of rainy periods from ground based microwave radiometry

AbstractIn this paper the authors present the results of a study aiming at detecting rainy data in measurements collected by a dual band ground-based radiometer.The proposed criterion is based on the ratio of the brightness temperatures observed in the 20–30 GHz band without need of any ancillary information. A major result obtained from the probability density of the ratio computed over one month of data is the identification of threshold values between clear sky, cloudy sky and rainy sky, respectively. A linear fit performed by using radiometric data and concurrent rain gauge measurements shows a correlation coefficient equal to 0.56 between the temperature ratio and the observed precipitation

Late Holocene landscape change history related to the Alpine Fault determined from drowned forests in Lake Poerua, Westland, New Zealand

Lake Poerua is a small, shallow lake that abuts the scarp of the Alpine Fault on the West Coast of New Zealand’s South Island. Radiocarbon dates from drowned podocarp trees on the lake floor, a sediment core from a rangefront alluvial fan, and living tree ring ages have been used to deduce the late Holocene history of the lake. Remnant drowned stumps of kahikatea (Dacrycarpus dacrydioides) at 1.7–1.9m water depth yield a preferred time-ofdeath age at 1766–1807 AD, while a dryland podocarp and kahikatea stumps at 2.4–2.6m yield preferred time-of-death ages of ca. 1459–1626 AD. These age ranges are matched to, but offset from, the timings of Alpine Fault rupture events at ca. 1717 AD, and either ca. 1615 or 1430 AD. Alluvial fan detritus dated from a core into the toe of a rangefront alluvial fan, at an equivalent depth to the maximum depth of the modern lake (6.7 m), yields a calibrated age of AD 1223–1413. This age is similar to the timing of an earlier Alpine Fault rupture event at ca. 1230AD±50 yr. Kahikatea trees growing on rangefront fans give ages of up to 270 yr, which is consistent with alluvial fan aggradation following the 1717AD earthquake. The elevation levels of the lake and fan imply a causal and chronological link between lake-level rise and Alpine Fault rupture. The results of this study suggest that the growth of large, coalescing alluvial fans (Dry and Evans Creek fans) originating from landslides within the rangefront of the Alpine Fault and the rise in the level of Lake Poerua may occur within a decade or so of large Alpine Fault earthquakes that rupture adjacent to this area. These rises have in turn drowned lowland forests that fringed the lake. Radiocarbon chronologies built using OxCal show that a series of massive landscape changes beginning with fault rupture, followed by landsliding, fan sedimentation and lake expansion. However, drowned Kahikatea trees may be poor candidates for intimately dating these events, as they may be able to tolerate water for several decades after metre-scale lake level rises have occurred

Towards a seismogenic source model of the Dinarides

Geology-based seismogenic source models are becoming the fundamental input for seismic hazard assessment at the scale of an entire country. In this work, we will illustrate in simple steps the complex process that leads from basic data to a fully-fledged seismogenic source model of the Dinaride thrust belt, running along coastal Croatia, Montenegro and part of Albania. We started from a layer of basic geological and structural data and explored a wide range of indicators of recent tectonic activity, such as drainage anomalies/diversions and displaced or warped geological markers. We then analyzed the interplay of these indicators with known or prospective tectonic structures. To the picture thus obtained, we added a layer with a revised historical seismic catalog and selected a few earthquakes for which we re-estimate epicenter and magnitude. At the end of our analyses we combined all these data in a structured GIS database. With these data at hand, we also compared the longer-term indicators with present-day stress/strain data such as GPS velocities and earthquake focal solutions. Following the approach already developed for the construction of the Database of Individual Seismogenic Sources for Italy, we developed a seismogenic source model for the Dinarides in which the better constrained seismogenic faults have been mapped and parameterized and made ready for use in seismic hazard practice. We believe that our experience in the Dinarides will become useful in unifying and formalizing the process of constructing seismic source models in other countries

The rna-binding ubiquitin ligase mex3a affects glioblastoma tumorigenesis by inducing ubiquitylation and degradation of rig-i

Glioblastoma multiforme (GB) is the most malignant primary brain tumor in humans, with an overall survival of approximatively 15 months. The molecular heterogeneity of GB, as well as its rapid progression, invasiveness and the occurrence of drug-resistant cancer stem cells, limits the efficacy of the current treatments. In order to develop an innovative therapeutic strategy, it is mandatory to identify and characterize new molecular players responsible for the GB malignant phenotype. In this study, the RNA-binding ubiquitin ligase MEX3A was selected from a gene expression analysis performed on publicly available datasets, to assess its biological and still-unknown activity in GB tumorigenesis. We find that MEX3A is strongly up-regulated in GB specimens, and this correlates with very low protein levels of RIG-I, a tumor suppressor involved in differentiation, apoptosis and innate immune response. We demonstrate that MEX3A binds RIG-I and induces its ubiquitylation and proteasome-dependent degradation. Further, the genetic depletion of MEX3A leads to an increase of RIG-I protein levels and results in the suppression of GB cell growth. Our findings unveil a novel molecular mechanism involved in GB tumorigenesis and suggest MEX3A and RIG-I as promising therapeutic targets in GB