Concerted and stepwise proton-coupled electron transfers in aquo/hydroxo complex couples in water: oxidative electrochemistry of [Os(II)(bpy)(2)(py)(OH(2))](2+)

Successive oxidation of transition metal(II) aqua complexes (M(II)OH(2) to M(III)OH) is a domain in which proton-coupled electron transfer reactions are extremely common. The mechanism of these PCET reactions-concerted or stepwise-is an important issue in the understanding and design of natural or artificial systems catalyzing the formation of dioxygen by four-electron oxidation of water. Concerted proton-coupled electron transfer from an aqua metal(II) to a hydroxo metal(III) complex requires the close proximity of a proton-accepting group with a pK value between those of the aqua complexes. Otherwise, stepwise electron-proton or proton-electron pathways involving high-energy intermediates are followed. Concerted proton-electron pathways involving water as proton-acceptor or proton-donor group are inefficient. Cyclic voltammetry of the title complex in buffered aqueous solution and re-examination of previous results for the same complex attached to an electrode surface are used to establish these conclusions, which provide a starting point on the route to higher degrees of oxidation, such as those involved in the catalysis of water oxidation.     

The numerical integration of relative equilibrium solutions. The nonlinear Schrodinger equation

We analyse different error propagation mechanisms for conservativeand nonconservative time-integrators of nonlinear Schrödingerequations. We use a geometric approach based on interpretingwaves as relative equilibria.     

Picomolar quantitation of free sulfite in foods by means of [57Co]hydroxocobalamin and radiometric chromatography of [57Co]sulfitocobalamin. Method, applications and significance of coexisting sulfides

The concentration dependent reaction of sulfite with 57Co-labeled hydroxocobalamin (OH57CoCbl) to produce a sulfitocobalamin (SO(3)57CoCbl) adduct served as a quantification strategy for foodborne sulfite residues freely extracted into pH 5.2, 0.05 M acetate buffer. SO(3)57CoCbl was then resolved using SP-Sephadex C-25 gel chromatography and its radiometric detection allowed calculation of a standard logit plot from which unknown sulfite concentrations could be determined. The sulfite detection range was 6.0 nM-0.3 pM with respective relative standard deviations of 4.4-29.4% for 50-microl samples. Individual incidences of foodborne sulfite intolerances provoked by L-cysteine or sulfite additive use in bakery products, which remained undetected using conventional sulfite analytical methods, underscored the quantitative value of the method. The analytical significance and occurrences of detectable sulfides coexisting with foodborne sulfite residues was also addressed.     

Influence of Structural Parameters on the Self‐Association Properties of Anti‐HIV Catanionic Dendrimers

The self‐association properties of anti‐HIV catanionic dendrimers as multivalent galactosylceramide (GalCer)‐derived inhibitors are presented. The study was designed to elucidate the origin of the relatively high cytotoxicity values of these anti‐HIV catanionic dendrimers, which have previously been found to exhibit in vitro anti‐HIV activity in the submicromolar range. The physicochemical properties of these catanionic dendrimers were studied to tentatively correlate the structural parameters with self‐association and biological properties. We can conclude from this study that the absence of correlation between the hydrophobicity and the cytotoxicity of the catanionic systems could be explained by the partial segregation of the different partners of the catanionic entities.     

Comparison of stability predictions and simulated unfolding of rhodopsin structures

Developing a better mechanistic understanding of membrane protein folding is urgently needed because of the discovery of an increasing number of human diseases, where membrane protein instability and misfolding is involved. Towards this goal, we investigated folding and stability of 7-transmembrane (TM) helical bundles by computational methods. We compared the results of three different algorithms for predicting changes in stability of proteins against an experimental mutation dataset obtained for bacteriorhodopsin (BR) and mammalian rhodopsin and find that 61.6% and 70.6% of the mutation results can potentially be explained by known local contributors to the stability of the folded state of BR and mammalian rhodopsin, respectively. To obtain further information on the predicted folding pathway of 7-TM proteins, we conducted simulated thermal unfolding experiments of all available rhodopsin structures with resolution better than 3 angstroms using the Floppy Inclusions and Rigid Substructure Topography (FIRST) method (Jacobs, D. J., A. J. Rader, L. A. Kuhn and M. F. Thorpe [2001] Proteins 44, 150) described previously for a single mammalian rhodopsin structure (Rader et al. [2004] PNAS 101, 7246). In statistical comparison we found that structures of mammalian rhodopsin have a stability core that is characterized by long-range interactions involving amino acids close in space but distant in sequence comprising positions from both extracellular loop and TM regions. In contrast, BR-simulated unfolding does not reveal such a core but is dominated by interactions within individual and groups of TM helices, consistent with the two-stage hypothesis of membrane protein folding. Similar results were obtained for halo- and sensory rhodopsins as for BRs. However, the average folding core energies of sensory rhodopsins were in between those observed for mammalian rhodopsins and BRs hinting at a possible evolution of these structures toward a rhodopsin-like behavior. These results support the conclusion that although the two-stage model can explain the mechanisms of folding and stability of BR, it fails to account for the folding and stability of mammalian rhodopsin, even though the two proteins are structurally related.     

Integral resource capacity planning for inpatient care services based on bed census predictions by hour

The design and operations of inpatient care facilities are typically largely historically shaped. A better match with the changing environment is often possible, and even inevitable due to the pressure on hospital budgets. Effectively organizing inpatient care requires simultaneous consideration of several interrelated planning issues. Also, coordination with upstream departments like the operating theatre and the emergency department is much-needed. We present a generic analytical approach to predict bed census on nursing wards by hour, as a function of the Master Surgical Schedule and arrival patterns of emergency patients. Along these predictions, insight is gained on the impact of strategic (ie, case mix, care unit size, care unit partitioning), tactical (ie, allocation of operating room time, misplacement rules), and operational decisions (ie, time of admission/discharge). The method is used in the Academic Medical Center Amsterdam as a decision-support tool in a complete redesign of the inpatient care operations.