A Versatile Pseudo-Random Noise Generator

A detailed design is presented for a digital pseudo-random noise generator. The instrument is built with standard integrated circuits. It produces both binary noise (pseudo-random binary sequences) and white Gaussian noise of variable bandwidth. By setting front panel switches to match tabulated octal codes, one may select a vast number of independent noise programs

Targeting GIRK Channels for the Development of New Therapeutic Agents

G protein-coupled inward rectifier K+ (GIRK) channels represent novel targets for the development of new therapeutic agents. GIRK channels are activated by a large number of G protein-coupled receptors (GPCRs) and regulate the electrical activity of neurons, cardiac myocytes, and β-pancreatic cells. Abnormalities in GIRK channel function have been implicated in the patho-physiology of neuropathic pain, drug addiction, cardiac arrhythmias, and other disorders. However, the pharmacology of these channels remains largely unexplored. In this paper we describe the development of a screening assay for identifying new modulators of neuronal and cardiac GIRK channels. Pituitary (AtT20) and cardiac (HL-1) cell lines expressing GIRK channels were cultured in 96-well plates, loaded with oxonol membrane potential-sensitive dyes and measured using a fluorescent imaging plate reader. Activation of the endogenous GPCRs in the cells caused a rapid, time-dependent decrease in the fluorescent signal; indicative of K+ efflux through the GIRK channels (GPCR stimulation versus control, Z′-factor = 0.5–0.7). As expected this signal was inhibited by addition of Ba2+ and the GIRK channel toxin tertiapin-Q. To test the utility of the assay for screening GIRK channel blockers, cells were incubated for 5 min with a compound library of Na+ and K+ channel modulators. Ion transporter inhibitors such as 5-(N,N-hexamethylene)-amiloride and SCH-28080 were identified as blockers of the GIRK channel at sub-micromolar concentrations. Thus, the screening assay will be useful for expanding the limited pharmacology of the GIRK channel and in developing new agents for the treatment of GIRK channelopathies

Feasibility of superconductivity in semiconductor superlatices

The objective of this thesis is to explore superconductivity in semiconductor superlattices of alternating hole and electron layers. The feasibility of superconductivity in semiconductor superlattices is based on a model formulated by Harshrnan and Mills. In this model, a semiconductor superlattice forms the layered electron and hole reservoirs of high transition temperature (high-Tc) superconductors. A GaAs-A1xGa1-xAs semiconductor structure is proposed which is predicted to superconduct at Tc = 2.0 K and may be analogous to the layered electronic structure of high-Tc superconductors. Formation of an alternating sequence of electron- and hole-populated quantum wells (an electron-hole superlattice) in a modulation-doped GaAs- A1xGa1-xAs superlattice is considered. In this superlattice, the distribution of carriers forms a three-dimensional Wigner lattice where the mean spacing between carriers in the x-y plane is the same as the periodic distance between wells in the superlattice. This geometrical relationship mimics a prominent property of optimally doped high - Tc superconductors. A Schrodinger-Poisson solver, developed by Snider, is applied to the problem of determining the appropriate semiconductor layers for creating equilibrium electron-hole superlattices in the GaAs-A1xGa1-xAs system. Formation of equilibrium electron-hole superlattices in modulation-doped GaAs-A1xGa1-xAs is studied by numerical simulations. Electron and heavy-hole states are induced by built-in electric fields in the absence of optical pumping, gate electrodes, or electrical contacts. The GaAs-A1xGa1-xAs structure and the feasibility of meeting all the criteria of the Harshman model for superconductivity is studied by self-consistent numerical simulation. In order to test the existence of superconductivity, the physics of sensor arrays and their ability to create synthetic images of semiconductor structures, is explored. Approximations are considered and practical applications in detecting superconductivity in superlattices are evaluated