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EphrinA1, a membrane-bound receptor tyrosine kinase ligand expressed in healthy cardiomyocytes, is lost in injured cells following myocardial infarction. Previously, we have reported that a single intramyocardial injection of chimeric ephrinA1-Fc at the time of ischemia reduced injury in the nonreperfused myocardium by 50% at 4 days post-MI by reducing apoptosis and inflammatory cell infiltration. In a clinically relevant model of acute ischemia (30min)/reperfusion (24hr or 4 days) injury, we now demonstrate that ephrinA1-Fc reduces infarct size by 46% and completely preserves cardiac function (ejection fraction, fractional shortening, and chamber dimensions) in the short-term (24hrs post-MI) as well as long-term (4 days). At 24 hours post-MI, diminished serum inflammatory cell chemoattractants in ephrinA1-Fc-treated mice reduces recruitment of neutrophils and leukocytes into the myocardium. Differences in relative expression levels of EphA-Rs are described in the context of their putative role in mediating cardioprotection. Validation by Western blotting of selected targets from mass spectrometry analyses of pooled samples of left ventricular tissue homogenates from mice that underwent 30min ischemia and 24hr of reperfusion (I/R) indicates that ephrinA1-Fc administration alters several regulators of signaling pathways that attenuate apoptosis, promote autophagy, and shift from FA metabolism in favor of increased glycolysis to optimize anaerobic ATP production. Taken together, reduced injury is due a combination of adaptive metabolic reprogramming, improved cell survival, and decreased inflammatory cell recruitment, suggesting that ephrinA1-Fc enhances the capacity of the heart to withstand an ischemic insult.

The miniaturization and integration of frequency-agile microwave circuits--relevant to electronically tunable filters, antennas, resonators and phase shifters--with microelectronics offers tantalizing device possibilities, yet requires thin films whose dielectric constant at gigahertz frequencies can be tuned by applying a quasi-static electric field. Appropriate systems such as BaxSr1-xTiO3 have a paraelectric-ferroelectric transition just below ambient temperature, providing high tunability. Unfortunately, such films suffer significant losses arising from defects. Recognizing that progress is stymied by dielectric loss, we start with a system with exceptionally low loss--Srn+1TinO3n+1 phases--in which (SrO)2 crystallographic shear planes provide an alternative to the formation of point defects for accommodating non-stoichiometry. Here we report the experimental realization of a highly tunable ground state arising from the emergence of a local ferroelectric instability in biaxially strained Srn+1TinO3n+1 phases with n ≥ 3 at frequencies up to 125 GHz. In contrast to traditional methods of modifying ferroelectrics-doping or strain-in this unique system an increase in the separation between the (SrO)2 planes, which can be achieved by changing n, bolsters the local ferroelectric instability. This new control parameter, n, can be exploited to achieve a figure of merit at room temperature that rivals all known tunable microwave dielectrics.

Ferroelectric ferromagnets are exceedingly rare, fundamentally interesting multiferroic materials that could give rise to new technologies in which the low power and high speed of field-effect electronics are combined with the permanence and routability of voltage-controlled ferromagnetism. Furthermore, the properties of the few compounds that simultaneously exhibit these phenomena are insignificant in comparison with those of useful ferroelectrics or ferromagnets: their spontaneous polarizations or magnetizations are smaller by a factor of 1,000 or more. The same holds for magnetic- or electric-field-induced multiferroics. Owing to the weak properties of single-phase multiferroics, composite and multilayer approaches involving strain-coupled piezoelectric and magnetostrictive components are the closest to application today. Recently, however, a new route to ferroelectric ferromagnets was proposed by which magnetically ordered insulators that are neither ferroelectric nor ferromagnetic are transformed into ferroelectric ferromagnets using a single control parameter, strain. The system targeted, EuTiO(3), was predicted to exhibit strong ferromagnetism (spontaneous magnetization, approximately 7 Bohr magnetons per Eu) and strong ferroelectricity (spontaneous polarization, approximately 10 microC cm(-2)) simultaneously under large biaxial compressive strain. These values are orders of magnitude higher than those of any known ferroelectric ferromagnet and rival the best materials that are solely ferroelectric or ferromagnetic. Hindered by the absence of an appropriate substrate to provide the desired compression we turned to tensile strain. Here we show both experimentally and theoretically the emergence of a multiferroic state under biaxial tension with the unexpected benefit that even lower strains are required, thereby allowing thicker high-quality crystalline films. This realization of a strong ferromagnetic ferroelectric points the way to high-temperature manifestations of this spin-lattice coupling mechanism. Our work demonstrates that a single experimental parameter, strain, simultaneously controls multiple order parameters and is a viable alternative tuning parameter to composition for creating multiferroics.