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The heterozygous Phospholamban p.Arg14del mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. This mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+ dynamics. Little is known about the physiological processes preceding induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we address these issues using a knock-in Phospholamban p.Arg14del zebrafish model. Hearts from adult zebrafish with this mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography reveals contractile variations before overt structural changes occur, which correlates at the cellular level with action potential duration alternans. These functional alterations are preceded by diminished Ca2+ transient amplitudes in embryonic hearts as well as an increase in diastolic Ca2+ level, slower Ca2+ transient decay and longer Ca2+ transients in cells of adult hearts. We find that istaroxime treatment ameliorates the in vivo Ca2+ dysregulation, rescues the cellular action potential duration alternans, while it improves cardiac relaxation. Thus, we present insight into the pathophysiology of Phospholamban p.Arg14del cardiomyopathy. Arrhythmogenic cardiomyopathy is a genetically inherited disease caused by deletion of an arginine in Phospholamban (PLN), a small protein that regulates intracellular calcium levels. Here the authors show that zebrafish with the PLN p.Arg14del mutation develop severe cardiomyopathy which is preceded by contractile dysfunction and altered calcium dynamics and istaroxime is identified as a small molecule that can rescues some of these phenotypes. [ABSTRACT FROM AUTHOR]

This article presents experimental data, and their comprehensive analysis, for a polystyrene foam (with an initial density of 0.623 g/cm3) subjected to large strains and high pressures. The data were obtained from unconfined uniaxial stress tests in compression (at two different strain rates), confined compression tests with compressive strains to almost 50%, and a tension test. The confinement for the compression tests consists of a steel cylinder with external strain gages to monitor the hoop strains due to the radial stresses from the compressed foam. The procedure used to analyze the data allows for a continuous determination of axial, radial and hoop stresses, pressure, and von Mises equivalent stress. A parametric finite element analysis was used to provide for the determination of the stresses from small strains to large strains approaching 50%. There is excellent agreement between test results for similar conditions, as well as the results from data obtained from the confined experiments with two different wall thicknesses. The strength (von Mises equivalent stress) is highly dependent on the pressure, but not as dependent on the strain. The strain rate has a significant effect on strength for the uniaxial stress tests, but only limited data were obtained. Constants were obtained for an existing computational model, and there is good correlation between the experimental data and the model. [ABSTRACT FROM AUTHOR]

Aluminum 5083 was tested using forward Taylor impact experiments for impact velocities ranging from 75 to 393 m/s, using stereo digital image correlation (DIC) at 320,000 Hz as the primary data collection method. The Taylor impact experiment is a simple method for evaluating the response of materials at high strain and strain rate, historically by using relationships between the material sample geometric profile after the experiment and yield stress. Initially, this limited Taylor impact experiments to qualitative studies, since the time-variance of the stress-strain state complicates analysis. A benefit of using DIC is that a single experiment sample provides quantitative information about the material deformation response at a wide range of strains and strain rates. DIC was used in this experimental program to measure the strain field, strain rate, and profile of the samples during impact. Peak strains approaching 80% and strain rates approaching 105/s were measured at the impact-end of the material samples at higher velocities (320 m/s and higher). Numerical simulations of the experiments were conducted using LS-DYNA and showed good time-resolved agreement with the experiment result strain and strain rate profiles from DIC. Highlights of the DIC data, including strain fields, time histories, and comparisons between experiments will be presented along with comparisons of the DIC data to the numerical analysis. [ABSTRACT FROM AUTHOR]

An extensive suite of experiments was conducted to characterize the mechanical response of an S-2 glass composite. The primary interest was the response of a 3-D composite, consisting of unidirectional (non-woven) layers of glass fibers interlaced by through-thickness Z-yarns. A plain-weave material was also characterized for comparison purposes. Additionally, epoxy-only specimens were fabricated to assist in understanding the contribution of the SC-15 epoxy resin in the response of the composite system. Two new specimen geometries (torsion and hourglass) were developed specifically for this characterization effort. The response of these specimens provides considerable insight into the failure mechanics of the plain weave and 3-D weave composites. It was shown that the matrix material has an elastic-plastic response, but with different strengths in tension and torsion. The response of the composite in tension is controlled by the epoxy until failure at the glass-resin interface. The strength falls to zero for the plain-weave composite, but the Z-yarns can support tensile stress until the yarns begin to fail. The fibers contribute to the elastic stiffness in shear for the plain-weave material, but the failure strength in shear is the same as the matrix. The 3-D weave composite also fails at the failure strength of the matrix, but retains some shear strength because of the Z-yarns. [ABSTRACT FROM AUTHOR]

This article describes two techniques used to characterize intact and damaged soda-lime glass at pressures up to ∼2 GPa: triaxial compression and confined sleeve. The results of the characterization experiments are described for intact and damaged glass as a function of confinement pressure and interpreted in terms of two pressure-dependent constitutive models, Drucker-Prager and Mohr-Coulomb. An observation is that the slopes of the two models appear to be independent of the degree of damage (intact, predamaged and severely damaged specimens). It is also observed that there is a maximum strength for the damaged glass, i.e., there is a cap on the strength. The compressive response of soda-lime glass is compared to that of a borosilicate glass, and to flyer-plate impact data. [ABSTRACT FROM AUTHOR]

At the hundredth anniversary of the Tunguska event in Siberia it is appropriate to discuss measures to avoid such occurrences in the future. Recent discussions about detecting, tracking, cataloguing, and characterizing near-Earth objects (NEOs) center on objects larger than about 140 m in size. However, objects smaller than 100 m are more frequent and can cause significant regional destruction of civil infrastructures and population centers. The cosmic object responsible for the Tunguska event provides a graphic example: although it is thought to have been only about 50 to 60 m in size, it devastated an area of about 2000 km2. Ongoing surveys aimed at early detection of a potentially hazardous object (PHO: asteroid or comet nucleus that approaches the Earth’s orbit within 0.05 AU) are only a first step toward applying countermeasures to prevent an impact on Earth. Because “early” may mean only a few weeks or days in the case of a Tunguska-sized object or a longperiod comet, deflecting the object by changing its orbit is beyond the means of current technology, and destruction and dispersal of its fragments may be the only reasonable solution. Highly capable countermeasures- always at the ready—are essential to defending against an object with such short warning time, and therefore short reaction time between discovery and impending impact. We present an outline for a comprehensive plan for countermeasures that includes smaller (Tunguska-sized) objects and long-period comets, focuses on short warning times, uses non-nuclear methods (e.g., hyper-velocity impactor devices and conventional explosives) whenever possible, uses nuclear munitions only when needed, and launches from the ground. The plan calls for international collaboration for action against a truly global threat. [ABSTRACT FROM AUTHOR]