Studies on the reconstitution of bovine erythrocyte superoxide dismutase : V. Preparation and properties of derivatives in which both zinc and copper sites contain copper

1. 1. We have developed a procedure for preparing derivatives of bovine superoxide dismutase in which primarily the Cu binding sites are occupied by Cu2+ (2 Cu2+-) and in which both the Zn and Cu binding sites are occupied by Cu2+ (4 Cu2+-).2. 2. The 2 Cu2+ protein shows approximately one-half the superoxide dismutase activity of an equivalent amount of native protein. A two-fold enhancement of the activity of 2 Cu2+-dismutase was observed upon occupation of the Zn sites either with Zn2+ or Cu2+.3. 3. The electron paramagnetic resonance spectrum of 4 Cu2+ protein was recorded over the temperature range 5-100 [deg]K and the results suggest an antiferromagnetic interaction between Cu2+ in the Zn site and Cu2+ in the Cu site having a coupling constant of approx. 52 cm-1.4. 4. The binuclear Cu2+ complex was found to accept only one electron from ferrocyanide.5. 5. One-half the total Cu+ of dithionite reduced 4 Cu+ protein was found to react rapidly with bathocupreine sulfonate whereas the other half reacted slowly. Reduced native protein did not react with bathocupreine sulfonate below 70 [deg]C.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22003/1/0000416.pd

Multi-Objective Pharmaceutical Portfolio Optimization under Uncertainty of Cost and Return

This paper presents the study of multi-objective optimization of a pharmaceutical portfolio when both cost and return values are uncertain. Decision makers in the pharmaceutical industry encounter several challenges in deciding the optimal selection of drug projects for their portfolio since they have to consider several key aspects such as a long product-development process split into multiple phases, high cost and low probability of success. Additionally, the optimization often involves more than a single objective (goal) with a non-deterministic nature. The aim of the study is to develop a stochastic multi-objective approach in the frame of chance-constrained goal programming. The application of the results of this study allows pharmaceutical decision makers to handle two goals simultaneously, where one objective is to achieve a target return and another is to keep the cost within a finite annual budget. Finally, the numerical results for portfolio optimization are presented and discussed