Targeting cell surface receptors with ligand-conjugated nanocrystals

To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT(3)) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.     

Doing Something about the Future

This paper is concerned with the need for more interdisciplinary, systems oriented, research directed towards major problems encountered by decision makers in industry and government; a need which is more difficult to meet in the face of traditional methods of organising knowledge and research. It emphasises the need to acknowledge the true complexity of the problems and the interactive nature of any effective research procedure. As an illustration, both of the need and the problems involved in meeting it, the development of a new program of research into problems of Management and Technology at the International Institute of Applied Systems Analysis, which is supported by seventeen nations of all political complexions, is analysed. The implication is that we can do something about the future, but we must be prepared to do.     

One step microelectroelution concentration method for efficient coupling of sodium dodecylsulfate gel electrophoresis and matrix-assisted laser desorption time-of-flight mass spectrometry for protein analysis

The coupling of the widely used separation technique of conventional sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) with the mass accuracy measurement capability of mass Spectrometry (MS) provides a very powerful analytical technique. However, at present, there is no simple, definitive method for coupling the two methods. Typically, separated proteins are extracted from the gel, either as the native protein or as a peptide mixture after in-gel proteolytic digestion, and then analyzed by mass Spectrometry. However, the various extraction techniques described previously have been labor intensive and require a large number of steps. The mass Spectrometry analysis of very low concentrations of in vivo derived proteins requires minimum sample handling and on-line concentration. Therefore, we have developed an efficient microelectroelution technique that is applied in a single step manner and contains an on-line concentration device. Initial results from this system have shown a high efficiency of analyte elution from the gel and a simple, robust technique for the coupling of SDS-containing gels with MALDI-TOF-MS analysis and a capability of analyzing proteins at the subpicomole level.     

XPS Analysis of Bridgman-grown CuInTe2 and of its Native Oxide

X-ray excited photoelectron spectroscopy is used to analyse the near-surface properties of CuInTe₂ single crystals grown by the vertical Bridgman method. It is found that keeping the crystals at room temperature in air for relatively short times is sufficient for the formation of an oxide layer which consists mainly of TeO₂. No detectable amounts of copper or indium oxides could be observed.     

Infrared Optical Characterization of Thermally Oxidized CuInSe2 Single Crystals

Infrared reflectivity spectra of thermally oxidized CuInSe₂ single crystals are measured at room temperature in the wavenumber range from 180 to 4000 cm⁻¹. A Kramers-Kronig analysis of the spectra reveals seven vibrational modes with frequencies which agree with mode frequencies in In₂O₃. No vibrational modes due to Cu–O and Se–O bonds could be observed. The results obtained are compared with previous studies of oxidized CuInSe₂ crystals.     

Photoacoustic Spectroscopy of Defect States in Etched and Air-annealed CuInSe2 Single Crystals

Photoacoustic spectra of cleaved, polished and etched, and air-annealed n-type CuInSe₂ single crystals are measured at different frequencies between 30 and 312 Hz. The spectra related to the bulk of the crystals exhibit five structures due to defects that are also present in p-type crystals. Polishing and etching as well as subsequent air annealing at 100, 200 and 300 °C reveal rather complex changes of the defect equilibrium in the near-surface region of the crystals which include both relative concentration changes of existing defects and creation of new defects. The results for polished and etched crystals correspond to trends expected from etching induced local modifications of the composition and structure as revealed by electron spectroscopies and ion channeling. Air annealing is found to affect all existing defects and to create up to five new defects which cannot be explained in terms of the related point defect model proposed by CAHEN and NOUFI.