Molecular Dynamics Studies of Bacteriorhodopsin's Photocycles

The availability of the structure of bacteriorhodopsin from electron microscopy studies has opened up the possibility of exploring the proton pump mechanism of this protein by means of molecular dynamics simulations. In this review we summarize earlier theoretical investigations of the photocycle of bacteriorhodopsin including relevant quantum chemistry studies of retinal, structure refinement, molecular dynamics simulations, and evaluation of pK_a values. We then review a series of recent modeling efforts which refined the structure of bacteriorhodopsin adding internal water, and which studied the nature of the J intermediate and the likely geometry of the K₅₉₀ and L₅₅₀ intermediates (strongly distorted 13-cis) as well as the sequence of retinal geometry and protein conformational transitions which are conventionally summarized as the M₄₁₂ intermediate. We also review simulations of the photocycle of light-adapted bacteriorhodopsin at T=77 K and of the photocycle of dark-adapted bacteriorhodopsin, both cycles differing from the conventional photocycle through a nonfunctional (pure 13-cis) retinal geometry of the corresponding K₅₉₀ and L₅₅₀ states. The simulations demonstrate a potentially critical role of water and of minute reorientations of retinal's Schiff base nitrogen in controlling proton pumping in bR₅₆₈; the simulations also indicate the existence of heterogeneous photocycles. The results exemplify the important role of molecular dynamics simulations in extending investigations on bacteriorhodopsin to a level of detail which is presently beyond experimental resolution, but which needs to be known to resolve the pump mechanism of bacteriorhodopsin. Finally, we outline the major existing challenges in the field of bacteriorhodopsin modeling.     

Educational utilization of plato in chemical reaction engineering

This article described a senior level course in Chemical Reaction Engineering created for computer-based delivery by the PLATO educational computer system. The course is completely self-paced and requires mastery learning. Students select from educational materials presented via a self-paced textbook, computer-based tutorials and computer-based problems. In additions, sophisticated numerical analysis capabilities allow students to efficiently solve advanced-level problems. Student progress is managed by the PLATO system which gives all testing and maintains all records. Several advantages of this type of course delivery are discussed with emphasis on the interactive computer graphics. This approach is shown to modify the traditional approaches to the solution of engineering problems.     

Washout of accumulated testosterone in a watershed

Testosterone is constantly excreted into the environment by both human and animal sources but little is known about how it is transported in the environment. In this study, testosterone was measured in 15 sites in the Upper Jordan Valley after major rain events (238 samplings) for two consecutive rain seasons. The area consists of small farms, cattle pasture, fish ponds with some urban development. One liter samples were extracted on solid phase columns and the eluates measured using specific radio-immunoassay for testosterone and estrogen (estradiol + estrone). The first rain season was the first above average season after a 3-year period of well below average rainfall. It was found in the rain season of 2001/2002, that following a rain sequence of 131 mm/week there was an initial large increase in the concentration of testosterone (maximum 6 ng/l) accompanied by high estrogen (maximum 6 ng/l), which then gradually declined to non-detectable levels (< 0.3 ng/l) over a period of 3 months. These peaks originated from runoff from cattle pasture and fish pond effluent. Later peaks consisted only of testosterone that was moderately associated with sulfate (r2 = 0.53, P < 0.05) and somewhat associated with total phosphorus (r2 = 0.49, P < 0.1) indicating that the origin was leaching from the sulfurous peat soil. In the following rainy season, which had recorded rainfalls, no testosterone peaks above 1 ng/l were seen. We conclude that the testosterone accumulated in the Upper Jordan Valley was washed out in two stages, first as surface runoff from cattle pasture and then as discharge from the soil.     

Distinction of cervical cancer biopsies by use of infrared microspectroscopy and probabilistic neural networks

Fourier-transform infrared spectroscopy has shown alterations of spectral characteristics of cells and tissues as a result of carcinogenesis. The research reported here focuses on the diagnosis of cancer in formalin-fixed biopsied tissue for which immunochemistry is not possible and when PAP-smear results are to be confirmed. The data from two groups of patients (a control group and a group of patients diagnosed with cervical cancer) were analyzed. It was found that the glucose/phosphate ratio decreases (by 23-49%) and the RNA/DNA ratio increases (by 38-150%) in carcinogenic compared with normal tissue. Fourier-transform microspectroscopy was used to examine these tissues. This type of study in larger populations may help to set standards or classes with which to use treated biopsied tissue to predict the possibility of cancer. Probabilistic neural networks and statistical tests as parts of these biopsies predict the possibility of cancer with a high degree of accuracy (> 95%).     

Comparing software for the solution of systems of nonlinear algebraic equations arising in chemical engineering

Five codes for solving systems of nonlinear equations, which are available in the literature, are compared using 10 test problems. The test problems are representative of a variety of areas in chemical engineering. In the comparison, robustness and reliability of the programs are emphasized, but information regarding their effectiveness is also given. The results of this study give the chemical engineer clear guidelines concerning the method that should be used for solving a particular problem.     

Ianov pushdown schemes are contained in boolean recursive schemes

Summary The class of Ianov schemes augmented by a pushdown memory is effectively translatable into the class of right linear boolean monadic recursive schemes. This proves a conjecture of Tokura, Kasami and Furuta [3].