Single-channel currents in isolated patches of plasma membrane from basal surface of pancreatic acini

Precise localization and characterization of conductance pathways in glandular epithelia have so far proved difficult. The patch-clamp technique for high resolution current recording, which has already been applied successfully to a number of electrically excitable cells, can in principle overcome these difficulties. We now report measurements of single-channel currents from isolated patches of plasma membrane (inside-out) from the baso-lateral surface of collagenase-isolated rat and mouse pancreatic acini. We have identified a cation channel having a conductance of approximately 30 pS and a mean open time in the range 0.3-1 s which is dependent on internal calcium. The single-channel current-voltage relationship is linear and the mean open time independent of the membrane potential. These channels may, at least in part, account for the Ca2+-mediated neural and hormonal control of pancreatic acinar membrane conductance, which is probably responsible for the Ca2+-dependent acinar fluid secretion.     

Conformational searching methods for small molecules. II. Genetic algorithm approach

We demonstrate the use of a genetic algorithm (GA) search procedure for finding low-energy conformations of small to medium organic molecules (1–12 rotatable bonds). GAS are in a class of biologically motivated optimization methods that evolve a population of individuals where individuals who are more “fit” have a higher probability of surviving into subsequent generations. Here, an individual is a conformation of a given molecule and the fitness is the molecule's conformational energy. In the course of a simulated evolution, the population produces conformations having increasingly lower energy. We test the GA method on a suite of 72 molecules and compare the performance against the CSEARCH algorithm in Sybyl. For molecules with more than eight rotatable bonds, the GA method is more efficient computationally and as the number of rotatable bonds increases the relative efficiency of the GA method grows. The GA method also found energies equal to or lower than the energy of the relaxed crystal structure in the large majority of cases. © John Wiley & Sons, Inc.     

Nonperturbative quantum calculation of the index of refraction of multilevel systems

We calculate the index of refraction (n) nonperturbatively for a multilevel ladder of states, and show that the dependence of n on the strength of an applied laser field departs qualitatively from that expected for a two-level system and employed in previous phenomenological models of self-focusing.     

The use of an algorithmic method for small molecule superimpositions in the design of antiviral agents

Summary The inability to reliably predict relative orientations of drug molecules within our series of antipicornavirus agents has severely limited the usefulness of available structure-activity data in the drug design process. A reported method of overlapping molecules has been evaluated to see if it could provide a solution to this problem. Although it initially succeeded remarkably well with a series of molecules whose bound X-ray structures were known, this success was shown to be only a function of the bound conformation of these molecules. Thus, this method did not provide a general solution to the problem at hand.     

Rotational sidebands in 166Er

Rotational sidebands in ¹⁶⁶Er were observed using the 24 MeV ¹⁶⁴Dy(α, 2nγ) reactions. The ground-state band was observed up to spin 16⁺ and does not backbend. A strong backbend is, however, observed in a K^π = (O⁺) sideband, indicating that the 12⁺ state of the previously unknown S-band is at 2656 keV. The γ-band shows significant rotational alignment above I = 10⁺. Levels of at least two negative-parity bands, one of which is primarily the K^π = 2^? octupole vibration, are also observed.     

A novel class II MHC molecule with unusual tissue distribution.

The repertoire of mature class II-restricted T cells is generated through a complex process of selection whereby early T cells confront class II molecules in the thymus, especially on epithelial cells. Expression of class II molecules on such cells is prominent both in the cortex and in the medulla. We have identified a novel class II molecule, H-20, which is expressed only in epithelial cells of the thymic medulla and in B cells. The unusual tissue distribution and the nonpolymorphic nature of H-20 suggest that its function is different from that of classical class II molecules.     

Photoacoustic spectroscopy investigation of radiationless relaxation processes of Cr3 in crystals

It is shown to be possible to identify dominant modes of radiationless relaxation of ions in crystals by comparing photoacoustic spectra with fluorescence excitation spectra. The dominant decay mode for Cr³⁺ in MgO is shown to be quite different from that found in ruby.