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Chloroquine resistance (CQR) in Plasmodium falciparum is associated with multiple mutations in the digestive vacuole membrane protein PfCRT. The chloroquine-sensitive (CQS) 106/1 line of P. falciparum has six of seven PfCRT mutations consistently found in CQR parasites from Asia and Africa. The missing mutation at position 76 (K76T in reported population surveys) may therefore be critical to CQR. To test this hypothesis, we exposed 106/1 populations (10(9)-10(10) parasites) to a chloroquine (CQ) concentration lethal to CQS parasites. In multiple independent experiments, surviving CQR parasites were detected in the cultures after 28 to 42 days. These parasites showed novel K76N or K76I PfCRT mutations and corresponding CQ IC(50) values that were approximately 8- and 12-fold higher than that of the original 106/1 IC(50). A distinctive feature of the K76I line relative to 106/1 parasites was their greatly increased sensitivity to quinine (QN) but reduced sensitivity to its enantiomer quinidine (QD), indicative of a unique stereospecific response not observed in other CQR lines. Furthermore, verapamil had the remarkable effect of antagonizing the QN response while potentiating the QD response of K76I parasites. In our single-step drug selection protocol, the probability of the simultaneous selection of two specific mutations required for CQR is extremely small. We conclude that the K76N or K76I change added to the other pre-existing mutations in the 106/1 PfCRT protein was responsible for CQR. The various mutations that have now been documented at PfCRT position 76 (K76T, K76N, K76I) suggest that the loss of lysine is central to the CQR mechanism.

The surface stoichiometry and reconstruction of GaP (001) are investigated by means of reflection high-energy electron diffraction and surface photo-absorption. The experiments were carried out using a solid-source molecular beam epitaxy system with a cracker cell as a P source. When the amount of Ga supplied to the surface is over 2 monolayer (ML), the 2×4 reconstruction corresponding to the P-stabilized surface is observed in spite of the existence of excess Ga on the surface. The change of surface reconstruction may be interpreted as follows: the surface is a Ga-terminated structure up to 2 ML of Ga supply, then Ga atoms move to some nonperiodic sites such as Ga droplets.

Lead titanate particles of controlled size around the nanometer range were prepared by hydrolyzing a mixture of the constituent metal alkoxides. The hydrolysate powder was crystallized by calcination into a tetragonally distorted perovskite structure. The hydrolysate started to crystallize by calcination at 470° C for one hour and the increase of the particle size due to the coalescence began at about 530° C. The increase continued beyond 900° C. The particle calcined at temperatures higher than 700° C seemed to become poly-crystalline. X-ray analysis shows that the strain in the particle was less than 0.2%. The smallest size of a well crystallized particle was about 15 nm.