HDXFinder: automated analysis and data reporting of deuterium/hydrogen exchange mass spectrometry

Hydrogen/deuterium exchange in combination with mass spectrometry (H/D MS) is a sensitive technique for detection of changes in protein conformation and dynamics. However, wide application of H/D MS has been hindered, in part, by the lack of computational tools necessary for efficient analysis of the large data sets associated with this technique. We report a novel web-based application for automatic analysis of H/D MS experimental data. This application relies on the high resolution of mass spectrometers to extract all isotopic envelopes before correlating these envelopes with individual peptides. Although a fully automatic analysis is possible, a variety of graphical tools are included to aid in the verification of correlations and rankings of the isotopic peptide envelopes. As a demonstration, the rate constants for H/D exchange of peptides from rabbit muscle pyruvate kinase are mapped onto the structure of this protein.     

An Operations Research Approach to the Problem of the Sugarcane Selection

Selection for superior clones is the most important aspect of sugar cane improvement programs, and is a long and expensive process. While studies have investigated different components of selection independently, there has not been a whole system approach to improve the process. This study observes the problem as an integrated system, where if one parameter changes the state of the whole system changes. A computer based stochastic simulation model that accurately represents the selection was developed. This paper describes the simulation model, showing its accuracy as well as how a combination of dynamic programming and branch and bound can be applied to the model to optimise the selection system, giving a new application of these techniques. The model can be directly applied to any region targeted by sugarcane breeding programs or to other clonally propagated crops.     

Improving the Sensitivity of a Quartz Crystal Microbalance for Biosensing by Using Porous Gold

 A quartz crystal microbalance can be used as a biosensor if biological receptor molecules (ligands) are attached to the crystal. To improve the sensitivity, the surface area of the gold electrodes on the crystal was increased by rendering the electrodes porous. This increased the response up to a factor of 3. A protein model system with human anti-myoglobin as ligand and sheep skeletal myoglobin at different concentrations as analyte was used. The quartz crystal was mounted in a flow-cell, where immobilisation, binding and regeneration of the surface were carried out. The kinetics of the model system was monitored under various experimental conditions. Received February 2, 2000. Revision June 30, 2000.     

Total Synthesis of (+)-6-epi-Ophiobolin A

The ophiobolin sesterterpenes are notable plant pathogens which have recently elicited significant chemical and biological attention because of their intriguing carbogenic frameworks, reactive functionalities, and emerging anticancer profiles. Reported herein is a total synthesis of (+)-6-epi-ophiobolin A in 14 steps, a task which addresses construction of the synthetically challenging spirocyclic tetrahydrofuran motif as well as several other key stereochemical problems. This work demonstrates a streamlined synthetic platform to complex ophiobolins leveraging disparate termination modes of a radical polycyclization cascade for divergent elaboration and functionalization.     

Addressing the Structural Complexity of Fluorinated Glucose Analogues: Insight into Lipophilicities and Solvation Effects

In this work, we synthesized all mono-, di-, and trifluorinated glucopyranose analogues at positions C-2, C-3, C-4, and C-6. This systematic investigation allowed us to perform direct comparison of ¹⁹F resonances of fluorinated glucose analogues and also to determine their lipophilicities. Compounds with a fluorine atom at C-6 are usually the most hydrophilic, whereas those with vicinal polyfluorinated motifs are the most lipophilic. Finally, the solvation energies of fluorinated glucose analogues were assessed for the first time by using density functional theory. This method allowed the log P prediction of fluoroglucose analogues, which was comparable to the C log P values obtained from various web-based programs.     

Regioselective Hydrosilylation of Olefins Catalyzed by a Molecular Calcium Hydride Cation

Chemo‐ and regioselectivity are often difficult to control during olefin hydrosilylation catalyzed by d‐ and f‐block metal complexes. The cationic hydride of calcium [CaH]⁺ stabilized by an NNNN macrocycle was found to catalyze the regioselective hydrosilylation of aliphatic olefins to give anti‐Markovnikov products, while aryl‐substituted olefins were hydrosilyated with Markovnikov regioselectivity. Ethylene was efficiently hydrosilylated by primary and secondary hydrosilanes to give di‐ and monoethylated silanes. Aliphatic hydrosilanes were preferred over other commonly employed hydrosilanes: Arylsilanes such as PhSiH₃ underwent scrambling reactions promoted by the nucleophilic hydride, while alkoxy‐ and siloxy‐substituted hydrosilanes gave isolable alkoxy and siloxy calcium derivatives.     

A radial-partition fluoroimmunoassay for the detection of Hepatitis B surface antigen with the streptavidin/biotin complex

A sandwich technique based on the very affinity between avidin and biotin is used. Antibodies are covalently bound to glass-fibre on which the antigen is captured. The discs are then treated in sequence with monoclonal antibodies of high selectivity, species-specific anti-IgG (biotin-linked), streptavidin and β-galactosidase, (biotin-linked). The discs are then incubated with the substrate, 4-methylumbelliferyl-β-d-galactopyranoside and the fluorescence is measured in an automatic immunoassay system.     

Decision analysis models in reinsurance

Decision analysis models are developed and illustrated for the reinsurance (risk transfer) decisions made by insurance companies. Decision analytic models were found to be useful tools both for structuring multistage reinsurance decisions and for comparing alternative options. The insurer is faced with many possible choices involving reinsurance type and extent, and an expected utility model provided insight both as a screening device and as an evaluation criterion. Decision analytic models appeared to be superior to other approaches such as mean/variance and risk of ruin models both because of their flexibility and their more comprehensive treatment the important elements of the decision, namely the complete claims distribution, the cost of reinsurance and the insurer's risk attitude.     

Charge-transfer and water-mediated adsorption. III. Adsorption on tryptophan-substituted Sephadex and Sepharose

The adsorption of tyrosine, tryptophan and some related compounds on tryptophan and tryptophanyltryptophan gels is similar to but much stronger than that observed with the parent gel Sephadex G-25. The adsorption has been attributed mainly to charge transfer or redistribution of electrons and protons leading to pi-bonding and hydrogen bonding, in addition to hydrophobic adsorption. The participation of organized water surrounding the gel matrix, the ligands and the solute molecules has been considered. The application of this principle of adsorption has been exemplified by chromatographic experiments with a cellulase preparation of tryptophan-Sepharose 4B.     

NMR diffusion analysis of surfactant-humic substance interactions

Surfactants can be introduced into the environment through wastewater or by direct contamination. Understanding the fate and transport of surfactants in the environment is important in assessing their role as pollutants. Humic substances are complex heterogeneous mixtures of decomposition products of natural organic materials. They are environmentally important because they are known to solubilize and transport organic pollutants. Therefore humic substances are likely to affect the environmental fate of surfactants. Diffusion coefficients measured with pulsed-field gradient nuclear magnetic resonance spectroscopy are used in this study to examine the intermolecular interactions of the surfactants sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) in the presence of various humic substances. These results indicate that humic substances enhance the aggregation of SDS prior to micellization with a more pronounced effect observed for the more hydrophobic humic materials. The positively charged surfactant CTAB forms stable ion pairs with the humic substances.