Omecamtiv mecarbil (OM) is a pharmacological agent that augments cardiac contractile function by enhancing myofilament Ca sensitivity. Given that interventions that increase myofilament Ca sensitivity have the potential to alter length-dependent activation (LDA) of cardiac myofilaments, we tested the influence of OM on this fundamental property of the heart. This is significant not only because LDA is prominent in cardiac muscle but also because it contributes to the Frank-Starling law, a mechanism by which the heart increases stroke volume in response to an increase in venous return. We measured steady-state and dynamic contractile indices in detergent-skinned guinea pig (Cavia porcellus) cardiac muscle fibers in the absence and presence of 0.3 and 3.0 μM OM at two different sarcomere lengths (SLs), short SL (1.9 μm) and long SL (2.3 μm). Myofilament Ca sensitivity, as measured by pCa (-log of [Ca] concentration required for half-maximal activation), increased significantly at both short and long SLs in OM-treated fibers when compared to untreated fibers; however, the magnitude of increase in pCa was twofold greater at short SL than at long SL. A consequence of this greater increase in pCa at short SL was that pCa did not increase any further at long SL, suggesting that OM abolished the SL dependency of pCa. Furthermore, the SL dependency of rate constants of cross-bridge distortion dynamics (c) and force redevelopment (k) was abolished in 0.3-μM-OM-treated fibers. The negative impact of OM on the SL dependency of pCa, c, and k was also observed in 3.0-μM-OM-treated fibers, indicating that cooperative mechanisms linked to LDA were altered by the OM-mediated effects on cardiac myofilaments.

Electronic defects and exciton traps were studied in yttrium aluminum garnet (YAG) single crystals by wavelength and temperature resolved thermoluminescence (TL). Measurements were carried out from room temperature to 400 °C on a number of rare earth (RE) doped and undoped YAG crystals, and the trap parameters were determined. Although the TL emission spectrum is characteristic of the RE ion, the main trap levels are found to be characteristic of the undoped host crystal. Nevertheless, the thermal activation energies of the traps are slightly modified by doping. The trap kinetics are found to be of the first order in both undoped and Ce doped YAG single crystals indicating the absence of retrapping, which suggests that the traps and recombination centers exhibit a close spatial correlation. The effect of annealing on TL response suggests that some of the major traps are associated with oxygen vacancies.

Strong luminescence peaks were observed at 700 and 800 nm in undoped yttrium aluminum garnet (YAG) single crystals. They were attributed to low level of iron impurities as confirmed by Glow Discharge Mass Spectrometry analysis. The 800 nm was only excited by high energy band at 270 nm; the reason behind that was discussed. Photoluminescence measurements revealed a large number of luminescence peaks in all YAG crystals regardless of the growth conditions due to native defects and low-level impurities. These luminescence centers have significant effects on the optical properties of rare-earth doped YAG crystals and their performance in laser and scintillation applications. Excitons released in the lattice may be easily captured by iron ions instead of Ce3+ ions and the scintillation output is substantially decreased. Nevertheless, Undoped YAG crystals may have the potential to be developed into efficient scintillators

The F88L mutation in cardiac troponin T (TnTF88L) is associated with hypertrophic cardiomyopathy. Reda and Chandra reveal that it abolishes length-mediated increase in myofilament Ca2+ sensitivity and attenuates cooperative mechanisms governing length-dependent activation.

Optical absorption and photoluminescence (PL) measurements were performed on single crystals of undoped Y3Al5O12 (YAG) and a number of rare-earth-doped YAG to study the effect of dopant type and concentration, growth atmosphere, post-growth annealing and UV irradiation on the optical properties of YAG crystals. The presence of hydrogen in the growth atmosphere was found to be essential for enhancing the incorporation of Ce ions in the Ce3+ state in Ce-doped YAG (Ce : YAG). Annealing in air was shown to have no effect on the PL emission of Ce : YAG crystals. An absorption peak around 256 nm was observed in the undoped YAG and Ce : YAG crystals after air anneal at 1200 °C. Optical absorption and annealing experiments support the association of the 256 nm peak with Fe impurities and oxygen ions. UV irradiation modifies the valency of impurities and generates electronic defects leading to an increase in the optical density of YAG crystals. Optimizing the growth and annealing conditions is critical in order to develop Ce : YAG single crystals as efficient scintillators.