Multicolour correlative imaging using phosphor probes

Correlative light and electron microscopy exploits the advantages of optical methods, such as multicolour probes and their use in hydrated live biological samples, to locate functional units, which are then correlated with structural details that can be revealed by the superior resolution of electron microscopes. One difficulty is locating the area imaged by the electron beam in the much larger optical field of view. Multifunctional probes that can be imaged in both modalities and thus register the two images are required. Phosphor materials give cathodoluminescence (CL) optical emissions under electron excitation. Lanthanum phosphate containing thulium or terbium or europium emits narrow bands in the blue, green and red regions of the CL spectrum; they may be synthesised with very uniform-sized crystals in the 10- to 50-nm range. Such crystals can be imaged by CL in the electron microscope, at resolutions limited by the particle size, and with colour discrimination to identify different probes. These materials also give emissions in the optical microscope, by multiphoton excitation. They have been deposited on the surface of glioblastoma cells and imaged by CL. Gadolinium oxysulphide doped with terbium emits green photons by either ultraviolet or electron excitation. Sixty-nanometre crystals of this phosphor have been imaged in the atmospheric scanning electron microscope (JEOL ClairScope). This probe and microscope combination allow correlative imaging in hydrated samples. Phosphor probes should prove to be very useful in correlative light and electron microscopy, as fiducial markers to assist in image registration, and in high/super resolution imaging studies

The nitridation of ZnO nanowires

ZnO nanowires (NWs) with diameters of 50 to 250 nm and lengths of several micrometres have been grown by reactive vapour transport via the reaction of Zn with oxygen on 1 nm Au/Si(001) at 550°C under an inert flow of Ar. These exhibited clear peaks in the X-ray diffraction corresponding to the hexagonal wurtzite crystal structure of ZnO and a photoluminescence spectrum with a peak at 3.3 eV corresponding to band edge emission close to 3.2 eV determined from the abrupt onset in the absorption-transmission through ZnO NWs grown on 0.5 nm Au/quartz. We find that the post growth nitridation of ZnO NWs under a steady flow of NH3 at temperatures ≤600°C promotes the formation of a ZnO/Zn3N2 core-shell structure as suggested by the suppression of the peaks related to ZnO and the emergence of new ones corresponding to the cubic crystal structure of Zn3N2 while maintaining their integrity. Higher temperatures lead to the complete elimination of the ZnO NWs. We discuss the effect of nitridation time, flow of NH3, ramp rate and hydrogen on the conversion and propose a mechanism for the nitridation

Single Mode Lasing from Hybrid Hemispherical Microresonators

Enormous attention has been paid to optical microresonators which hold a great promise for microlasers as well as fundamental studies in cavity quantum electrodynamics. Here we demonstrate a three-dimensional (3D) hybrid microresonator combining self-assembled hemispherical structure with a planar reflector. By incorporating dye molecules into the hemisphere, optically pumped lasing phenomenon is observed at room temperature. We have studied the lasing behaviors with different cavity sizes, and particularly single longitudinal mode lasing from hemispheres with diameter ∼15 μm is achieved. Detailed characterizations indicate that the lasing modes shift under varying pump densities, which can be well-explained by frequency shift and mode hopping. This work provides a versatile approach for 3D confined microresonators and opens an opportunity to realize tunable single mode microlasers

Human physiologically based pharmacokinetic model for propofol

BACKGROUND: Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK) model for propofol. METHODS: PKQuest, a freely distributed software routine , was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1) the value of the propofol oil/water partition coefficient; 2) the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. RESULTS: The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance) is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters). The average weighted residual error (WRE) of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. CONCLUSION: A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a PBPK model is that it can be used to predict the changes in kinetics produced by variations in physiological parameters. As one example, the model simulation of the changes in pharmacokinetics for morbidly obese subjects is discussed