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Ba (Ti0.91Zr0.09) O3 ceramics doped with Bi2O3 and Li2O respectively were prepared by a solid phase reaction. The effect of A-site donor-acceptor doped on dielectric properties was investigated. Dielectric properties were measured from −30°C to 130°C at different frequencies. Relaxor behavior was observed with increasing additive oxides concentration. Additive oxides introduce structural disorder, causing perturbations like local electric field and strain. These perturbations reduce the long-range polar order resulting in relaxor behavior. The corresponding relaxor characteristics were determined and discussed according to the A-site substituted cation type.

Mutations D1-D59N and D1-D61E in the putative Ca2+-binding lumenal interhelical a-b loop of the photosystem II (PSII) D1 protein [Chu, H. A., Nguyen, A. P., and Debus (1995), Biochemistry 34, 5839-5858] were further characterized in terms of S-state cycling and photoactivation. Bare platinum electrode measurements of centrifugally deposited O2-evolving membranes isolated from the a-b loop mutants demonstrated a retarded appearance of O2 following single turnover flashes, although not to the extent of retardation seen in the Deltapsb0 mutant, which lacks the extrinsic manganese-stabilizing protein (MSP). Double flash measurements indicate that retarded O2 release in mutants coincides with a decrease in overall PSII turnover during the S3-[S4]-S0 transition. S2 and S3 decay measurements in the isolated membranes indicate that D1-D59N and D1-D61E have faster decays of these higher S-states in contrast to slowed decays in the Deltapsb0 mutant. Measurements of the flash interval dependence of photoactivation indicate that intermediates of photoactivation [light-dependent assembly of the (Mn)4 complex] are highly destabilized in the a-b loop mutants compared to both DeltapsbO and the wild-type: flash intervals of greater than 2 s result in the nearly complete decay of unstable photointermediate(s) in the D1-D59N and D1-D61E samples, whereas a similar loss does not occur until intervals even greater than 10 s in the DeltapsbO and wild-type samples. These results are consistent with a role for the residues D1-D59 and D1-D61 in modulating the redox properties of the higher S-states and, also, possibly in the binding the calcium ion involved in photoactivation.

The estrogen receptor (ER) is a potentially useful biological target for diagnosis and therapy in hormonally responsive human breast cancer. This protein is often overexpressed both on the membrane and on the nuclear compartment of breast cancer cells and therefore provides a mechanism for targeted drug delivery. Over the past 30 years, many research groups have attempted to exploit the high affinity and receptor selectivity of steroidal estrogens to deliver cytotoxic agents that by themselves lack selectivity. In this review, we describe the strategies and methods employed by those investigators in their efforts to develop steroid-drug conjugates with the goals of enhanced antiproliferative activity and ER-selectivity. In particular, the choices of steroid scaffolds and sites for drug conjugation have evolved as the understanding of role of ER in cell function has expanded. Present knowledge of the mechanism of action for estrogens and antiestrogens helps explain the failure of most efforts to achieve their stated objectives. The review culminates in the description of our program, which has produced the first conjugate that clearly has achieved those goals and provides an approach for developing new agents for future clinical use.