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As a leading cause of heart failure, postinfarction left ventricular remodeling represents an important target for therapeutic interventions. Mitogen-activated protein kinases regulate critical cellular processes including stress response and survival, but their role in left ventricular remodeling is unknown. In the present study, rats were subjected to myocardial infarction by ligating the left anterior descending coronary artery. Western blot and kinase assay analysis revealed an inactivation of p38 kinase after myocardial infarction. Local adenovirus-mediated cotransfection of wild-type (WT) p38 kinase and constitutively active MKK3b reduced infarct size (26+/-3% vs. 47+/-4%, P<0.05 vs. LacZ-treated control) associated with improved ejection fraction (66.9+/-5.5% vs. 44.4+/-4.0%, P<0.001), fractional shortening (30.2+/-2.1% vs. 19.7+/-2.2%, P<0.001), and decreased left ventricular diastolic diameter (8.5+/-0.4 mm vs. 9.5+/-0.2 mm, P<0.01). p38 kinase gene transfer increased capillary density (2423+/-107/mm(2) vs. 1934+/-86/mm(2), P<0.001) and resulted in microvessel enlargement in the ischemic border zone. Apoptosis (35+/-7 vs. 69+/-13 cells, P<0.01) and fibrosis (16+/-3% vs. 34+/-8%, P<0.05) were reduced, while the number of c-kit positive cardiac stem-like cells remained unchanged. These results indicate that reduced p38 signaling predisposes to adverse postinfarction remodeling. The rescue of failing myocardium with p38 kinase may be a potential new therapy for heart failure after myocardial infarction.

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This paper studies the energy efficiency and sum rate trade-off for coordinated beamforming in multi-cell multiuser multigroup multicast multiple-input single-output systems. We first consider a conventional network energy efficiency maximization (EEmax) problem by jointly optimizing the transmit beamformers and antennas selected to be used in transmission. We also account for per-antenna maximum power constraints to avoid non-linear distortion in power amplifiers and user-specific minimum rate constraints to guarantee certain service levels and fairness. To be energy-efficient, transmit antenna selection is employed. It eventually leads to a mixed-Boolean fractional program. We then propose two different approaches to solve this difficult problem. The first solution is based on a novel modeling technique that produces a tight continuous relaxation. The second approach is based on sparsity-inducing method, which does not require the introduction of any Boolean variable. We also investigate the trade-off between the energy efficiency and sum rate by proposing two different formulations. In the first formulation, we propose a new metric that is the ratio of the sum rate and the so-called weighted power. Specifically, this metric reduces to EEmax when the weight is 1, and to sum rate maximization when the weight is 0. In the other method, we treat the trade-off problem as a multi-objective optimization for which a scalarization approach is adopted. Numerical results illustrate significant achievable energy efficiency gains over the method where the antenna selection is not employed. The effect of antenna selection on the energy efficiency and sum rate trade-off is also demonstrated.

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