Query Complexity of Derivative-Free Optimization

This paper provides lower bounds on the convergence rate of Derivative Free Optimization (DFO) with noisy function evaluations, exposing a fundamental and unavoidable gap between the performance of algorithms with access to gradients and those with access to only function evaluations. However, there are situations in which DFO is unavoidable, and for such situations we propose a new DFO algorithm that is proved to be near optimal for the class of strongly convex objective functions. A distinctive feature of the algorithm is that it uses only Boolean-valued function comparisons, rather than function evaluations. This makes the algorithm useful in an even wider range of applications, such as optimization based on paired comparisons from human subjects, for example. We also show that regardless of whether DFO is based on noisy function evaluations or Boolean-valued function comparisons, the convergence rate is the same

Chelator-facilitated removal of iron from transferrin: Relevance to combined chelation therapy

Current iron chelation therapy consists primarily of DFO (desferrioxamine), which has to be administered via intravenous infusion, together with deferiprone and deferasirox, which are orally-active chelators. These chelators, although effective at decreasing the iron load, are associated with a number of side effects. Grady suggested that the combined administration of a smaller bidentate chelator and a larger hexadentate chelator, such as DFO, would result in greater iron removal than either chelator alone [Grady, Bardoukas and Giardina (1998) Blood 92, 16b]. This in turn could lead to a decrease in the chelator dose required. To test this hypothesis, the rate of iron transfer from a range of bidentate HPO (hydroxypyridin-4-one) chelators to DFO was monitored. Spectroscopic methods were utilized to monitor the decrease in the concentration of the Fe–HPO complex. Having established that the shuttling of iron from the bidentate chelator to DFO does occur under clinically relevant concentrations of chelator, studies were undertaken to evaluate whether this mechanism of transfer would apply to iron removal from transferrin. Again, the simultaneous presence of both a bidentate chelator and DFO was found to enhance the rate of iron chelation from transferrin at clinically relevant chelator levels. Deferiprone was found to be particularly effective at ‘shuttling’ iron from transferrin to DFO, probably as a result of its small size and relative low affinity for iron compared with other analogous HPO chelators

Increase of reactive oxygen species by desferrioxamine during experimental Chagas' disease.

Oxidative stress is common in inflammatory processes associated with many diseases including Chagas' disease. The aim of the present study was to evaluate, in a murine model, biomarkers of oxidative stress together with components of the antioxidant system in order to provide an overview of the mechanism of action of the iron chelator desferrioxamine (DFO). The study population comprised 48 male Swiss mice, half of which were treated daily by intraperitoneal injection of DFO over a 35-day period, while half were administered sterile water in a similar manner. On the 14th day of the experiment, 12 DFO-treated mice and an equal number of untreated mice were experimentally infected with Trypanosoma cruzi. Serum concentrations of nitric oxide and superoxide dismutase and hepatic levels of total glutathione, thiobarbituric acid reactive species and protein carbonyl, were determined on days 0, 7, 14 and 21 post-infection. The results obtained revealed that DFO enhances antioxidant activity in the host but also increases oxidative stress, indicating that the mode of action of the drug involves a positive contribution to the host together with an effect that is not beneficial to the parasite

Supply Management and Price Ceilings on Production Quota Values: Future or Folly?

This paper examines and contrasts two policies instituted by the Dairy Farmers of Ontario (DFO) in reaction to the escalation of production quota values on the provincial quota exchange, which regulates the transfer of dairy production quota among producers in the province of Ontario.Supply Management, DFO, Production Quota, Provincial Quota Exchange, Price ceiling, Progressive Transfer Assessment, Agricultural and Food Policy, Livestock Production/Industries, Production Economics,

Understanding the Impact of Meteorological Spatiotemporal Variability on Distant Focusing Overpressure Risk

Since the 1950s, the amplification of blast energy from explosions has been understood to be a significant hazard to public safety at launch ranges. Historically, the risk assessment of the Distant Focusing Overpressure (DFO) hazard started with a single temperature and wind profile (e.g., a radiosonde launch) as input to acoustic 1-D ray tracing models. By analyzing rays propagation and performing ray tracing, population centers under high DFO risk can be identified. Although this method is useful, less is known about how the blast waves can be focused when the spatiotemporal variability of the input profiles are considered. In summary, this work aims to consider how realistic atmospheric boundary layer variability (e.g., turbulence, land-surface contrasts) may affect blast waves propagation and focusing and, as a result, DFO risk assessment results