Coherent optical control of the spin of a single hole in an InAs/GaAs quantum dot.

We demonstrate coherent optical control of a single hole spin confined to an InAs/GaAs quantum dot. A superposition of hole-spin states is created by fast (10-100 ps) dissociation of a spin-polarized electron-hole pair. Full control of the hole spin is achieved by combining coherent rotations about two axes: Larmor precession of the hole spin about an external Voigt geometry magnetic field, and rotation about the optical axis due to the geometric phase shift induced by a picosecond laser pulse resonant with the hole-trion transition.

Phonon-induced Rabi-frequency renormalization of optically driven single InGaAs/GaAs quantum dots.

We study optically driven Rabi rotations of a quantum dot exciton transition between 5 and 50 K, and for pulse areas of up to 14π. In a high driving field regime, the decay of the Rabi rotations is nonmonotonic, and the period decreases with pulse area and increases with temperature. By comparing the experiments to a weak-coupling model of the exciton-phonon interaction, we demonstrate that the observed renormalization of the Rabi frequency is induced by fluctuations in the bath of longitudinal acoustic phonons, an effect that is a phonon analogy of the Lamb shift.

Beating of exciton-dressed states in a single semiconductor InGaAs/GaAs quantum dot.

We report picosecond control of excitonic dressed states in a single semiconductor quantum dot. A strong laser pulse couples the exciton and biexciton states, to form an Autler-Townes doublet of the neutral exciton transition. The Rabi-splitting, and hence the admixture of the dressed states follows the envelope of the picosecond control laser. We create a superposition of dressed states, and observe the resulting beat: a direct measurement of a Rabi oscillation in time delay rather than the usual power domain.

Fast optical preparation, control, and readout of a single quantum dot spin.

We propose and demonstrate the sequential initialization, optical control, and readout of a single spin trapped in a semiconductor quantum dot. Hole spin preparation is achieved through ionization of a resonantly excited electron-hole pair. Optical control is observed as a coherent Rabi rotation between the hole and charged-exciton states, which is conditional on the initial hole spin state. The spin-selective creation of the charged exciton provides a photocurrent readout of the hole spin state.

Factors affecting patient compliance with anti-tuberculosis chemotherapy using the directly observed treatment, short-course strategy (DOTS).

SETTING: Kota Kinabalu and surrounding communities in Sabah, Malaysia. OBJECTIVES: To establish factors affecting compliance of patients with anti-tuberculosis chemotherapy, their knowledge of the disease, and views on improving the DOTS strategy. DESIGN: Interviews with compliant patients attending clinics for DOTS treatment and with non-compliant patients in their homes, in August and September 2000. RESULTS: A total of 63 compliant and 23 non-compliant patients were interviewed. For non-compliant patients, reaching the treatment centre entailed greater cost (P < 0.005) and travel time (P < 0.005) compared to compliant patients. Cost of transport was the reason most frequently given for non-attendance. Non-compliant patients were more likely to have completed secondary education (P < 0.05), and to be working (P < 0.01). More non-compliant patients had family members who had had the disease (P < 0.01). There was no difference between the groups for overall tuberculosis knowledge scores; however, non-compliant patients were more likely to think that treatment could be stopped once they were symptom free (P < 0.01). Most patients (73%) felt that the DOTS system could be improved by provision of more information about tuberculosis. CONCLUSION: Compliance with DOTS in the Kota Kinabalu area is affected by travel expenses, time spent travelling to treatment centres, and having family members who have had the disease. Patients would like more information on tuberculosis.

Variation in cytokines induced by particles from different prosthetic materials.

Particles of prosthetic material stimulate macrophages to release cytokines, which may cause bone loss and loosening of the prosthesis. This study investigates the possibility that particles of different prosthetic materials may induce different cytokines and thus have different effects on bone remodeling. The in vitro response of human monocytes to particles of cast and forged cobalt chrome alloy, stainless steel, and titanium aluminum vanadium alloy were compared. There was no difference in the biologic response to cobalt-chrome particles derived from cast or forged material. Cobalt-chrome particles were toxic to the cells, but titanium aluminum vanadium particles did not affect cell viability. Stainless steel particles were approximately 10 times more toxic than were cobalt-chrome particles. All particles induced the release of tumor necrosis factor and interleukin 1 beta; stainless steel particles were the most potent stimulators of interleukin 1 beta; titanium aluminum vanadium particles were the strongest stimulators of interleukin 6 and prostaglandin 2. The study showed that particles derived from prosthetic materials of different metal compositions can elicit significantly different biologic responses. Understanding these different responses may help identify materials better suited for prostheses.

The interaction of the NK1 receptor antagonist CP-96,345 with L-type calcium channels and its functional consequences.

1. We investigated the effects of the non-peptide NK1 receptor antagonist, CP-96,345, its inactive enantiomer CP-96,344, and the racemic mixture (+/-)-CP-96,345, on the binding of [3H]-nimodipine and [3H]-diltiazem to L-type calcium channels in rat cerebral cortex membranes. In isolated peripheral tissues containing tachykinin receptors, the effects of (+/-)-CP-96,345 have been compared with those of diltiazem. 2. In guinea-pig trachea, (+/-)-CP-96,345 produced antagonism of responses to the selective NK1 agonists [Sar9, Met(O2)11]SP and substance P-methyl ester that was apparently competitive in nature (pKB 7.0-7.5), while in guinea-pig ileum the antagonism was not surmountable. 3. The reduction of maximum responses by (+/-)-CP-96,345 in the guinea-pig ileum was not selective; it was obtained with muscarinic agonists and other agents, and was also observed in the portal vein of the rat where NK1 receptors are not present. 4. The tissue-specific reduction of maximum responses by (+/-)-CP-96,345 in ileum was reproduced by diltiazem. 5. (+/-)-CP-96,345 produced a concentration-dependent enhancement of [3H]-nimodipine binding to rat cerebral cortex membranes with a maximal stimulation of 186 +/- 29% above control (EC50 83.2 nM). Scatchard analysis revealed that (+/-)-CP-96,345 increased the affinity of [3H]-nimodipine for its binding sites without affecting Bmax (control: KD = 0.32 nM; with 100 nM (+/-)-CP-96,345: KD = 0.074 nM). 6. CP-96,345, CP-96,344, and the racemate all inhibited [3H]-diltiazem binding in rat cerebral cortex membranes with Ki values of 22.5 nM, 34.5 nM and 29.9 nM respectively; a similar value was obtained for diltiazem itself (33.6 nM). In comparison, CP-96,345 and ( +/- )-CP-96,345 inhibited the binding of[125I]-Bolton-Hunter-conjugated substance P in this tissue with Ki values of 59.6 nM and 82.0 nM respectively, while CP-96,344 had no measurable affinity (IC50> 10 microM).7. Substance P and a range of ligands selective for NK1, NK2, or NK3 receptors had no significant effect at 10 microM on either [3H]-diltiazem or [3H]-nimodipine binding.8. The results indicate that in addition to possessing affinity for the NK1 receptor, the non-peptide antagonist, CP-96,345, displays high affinity for [3H]-diltiazem binding sites on L-type calcium channels.The functional effect that may be observed in integrated models will be a consequence of either property, or be a composite effect of NK1 receptor antagonism and L-channel blockade.

Characterization of CCK receptors in a novel smooth muscle preparation from the guinea-pig stomach by use of the selective antagonists CI-988, L-365,260 and devazepide.

1. The cholecystokinin receptors mediating motor responses in a novel smooth muscle preparation from the corpus region of the guinea-pig stomach have been characterized by use of five agonist peptides and the antagonists CI-988, L-365,260 and devazepide. 2. Mucosa-denuded strips of circular muscle were contracted in a concentration-dependent manner by the five cholecystokinin (CCK)-related peptides CCK-8S, pentagastrin, gastrin-I, CCK-8US and CCK-4. 3. CI-988 was a powerful antagonist of the response to pentagastrin with an affinity (pKB = 9.49) similar to that obtained in CCKB receptor binding assays. With CCK-8S as the agonist, CI-988 was approximately 1000 fold less powerful as an antagonist. 4. Devazepide powerfully blocked responses to CCK-8S with an affinity (pKB = 9.54) that was in agreement with reported functional data obtained in pancreatic amylase secretion studies, a system exhibiting CCKA receptor activity. Devazepide displayed lower affinity against pentagastrin than against CCK-8S. 5. CI-988 blocked responses to pentagastrin in an insurmountable manner in the presence of 3 nM devazepide; a concentration previously shown to block the CCKA receptor. The nature of the antagonism observed with L-365,260 was unaltered by the presence of devazepide. 6. The guinea-pig stomach corpus smooth muscle preparation contains both subtypes of CCK receptor and will be useful as a pharmacological tool for investigating the functional effects of novel CCK ligands.

CI-977, a novel and selective agonist for the kappa-opioid receptor.

1. CI-977 is a new, nonpeptide kappa-opioid compound that has been synthesized and its pharmacological properties determined in a series of in vitro and in vivo rodent models. 2. In a radioligand binding studies, with guinea-pig forebrain homogenates, CI-977 bound with high affinity to [3H]-U69593-labelled kappa-sites (Ki = 0.11 nM) but with low affinity to [3H]-[D-Ala2, MePhe4, Gly-ol5] enkephalin (DAMGO) labelled mu-sites (Ki = 99 nM) and [3H]-[D-Pen2.5]enkephalin (DPDPE) labelled delta-sites (Ki = 1.04 microM). CI-977 also bound with negligible affinity to [3H]-(+)-3-(1-propyl-3-piperi-dinyl)phenol (3-PPP) labelled sigma-sites (Ki = 1.9 microM) and [3H]-1-(1-[2-thienyl]cyclohexyl)piperidine (TCP) labelled PCP sites (Ki greater than 10 microM). 3. CI-977 produced a potent inhibition of the electrically-evoked contractions of the guinea-pig ileum and rabbit vas deferens with IC50 values of 0.087 nM and 3.3 nM, respectively. The pKB values for the opioid antagonists naloxone (7.6) and norbinaltorphimine (10.5) supported the kappa nature of the CI-977-mediated effects in the smooth muscle assays. 4. CI-977 was a potent antinociceptive agent against a mechanical noxious stimulus in rats following intravenous, intramuscular, subcutaneous and oral administration. CI-977 was also effective against mechanical and chemical noxious stimuli in the mouse but ineffective against a thermal stimulus. The antinociceptive effects produced by CI-977 were completely reversed by naloxone (1 mg kg-1, s.c.). 5. At doses close to those required to produce antinociception, CI-977 also caused a naloxone-reversible diuresis and inhibition of locomotor activity.6. The in vitro and in vivo pharmacological profile of CI-977 demonstrates that it is a potent and selective agonist at the Kappa-opioid receptor.

An in vitro profile of activity for the (+) and (-) enantiomers of spiradoline and PD117302.

Kappa- and mu-opioid binding site affinities of the kappa-selective ligand U62066 and its optical isomers, (+)-U63639 and (-)-U63640 were compared with those of the structurally related ligand PD117302 and its respective isomers, (+)-PD123497 and (-)-PD123475. The relative efficacies of each compound were also established using the guinea-pig ileum, rat and rabbit vas deferens smooth muscle bioassays. The specific opioid receptor mediating the agonist behaviour was determined in the guinea-pig ileum bioassay by obtaining pKB values for naloxone and for the kappa-selective antagonist nor-binaltorphimine. Both racemic compounds and the (-)-enantiomers displayed high selectivity for the kappa-receptor with (-)-PD123475 the most selective. The (+)-enantiomer, PD123497, was approximately equipotent at mu-/kappa-sites while (+)-U63639 displayed a 140-fold mu-receptor selectivity. Bioassay studies showed each compound to be interacting at the kappa-receptor, with the exception of (+)-U63639 which displayed a profile consistent with that of a weak mu-receptor agonist.