A new methodology for sensitivity and stability analysis of analytic network models

In this paper we develop a methodology to study the sensitivity and the stability of models built using the Analytic Network Process. We study two types of stability: core and solution stability. The former deals with finding the region of the perturbation space in which the initial solution (i.e., the alternative that is ranked first) obtained from the ANP model remains most preferred. The latter deals with finding the regions of the perturbation space in which the solutions that were not initially most preferred (i.e., alternatives that were not ranked first) become most preferred (i.e., they are ranked first). The methodology consists of three stages: generation of the perturbation space, finding the boundaries of the regions in the perturbation space in which the different alternatives are ranked first, and finding the stability regions.     

Transport engineering in microbial cell factories producing plant-specialized metabolites

Transport engineering strategies use altered expression of transporter proteins to change metabolite distribution within an organism. The production of plant specialized metabolites in microbial cell factories encounters a set of challenges that could benefit from the implementation of transport engineering technology. The range of challenges includes premature pathway termination due to secretion of intermediates, feedback inhibition due to inefficient export of final products, low yields in bioconversion processes due to inefficient import of precursors, and poor connectivity between subcellular compartments expressing different parts of complex biosynthetic pathways. We highlight the latest examples of transport engineering in microbial cell factories producing plant specialized metabolites, identify the current knowledge gap, and propose future research for advancing the field.     

Bioavailability and biotransformation of sulforaphane and erucin metabolites in different biological matrices determined by LC–MS–MS

The food-related isothiocyanate sulforaphane (SFN), a hydrolysis product of the secondary plant metabolite glucoraphanin, has been revealed to have cancer-preventive activity in experimental animals. However, these studies have often provided inconsistent results with regard to bioavailability, bioaccessibility, and outcome. This might be because the endogenous biotransformation of SFN metabolites to the structurally related erucin (ERN) metabolites has often not been taken into account. In this work, a fully validated liquid chromatography tandem mass spectrometry (LC–MS–MS) method was developed for the simultaneous determination of SFN and ERN metabolites in a variety of biological matrices. To reveal the importance of the biotransformation pathway, matrices including plasma, urine, liver, and kidney samples from mice and cell lysates derived from colon-cancer cell lines were included in this study. The LC–MS–MS method provides limits of detection from 1 nmol L^?1 to 25 nmol L^?1 and a mean recovery of 99 %. The intra and interday imprecision values are in the range 1–10 % and 2–13 %, respectively. Using LC–MS–MS, SFN and ERN metabolites were quantified in different matrices. The assay was successfully used to determine the biotransformation in all biological samples mentioned above. For a comprehensive analysis and evaluation of the potential health effects of SFN, it is necessary to consider all metabolites, including those formed by biotransformation of SFN to ERN and vice versa. Therefore, a sensitive and robust LC–MS–MS method was validated for the simultaneous quantification of mercapturic-acid-pathway metabolites of SFN and ERN.

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Graphical Abstract Biotransformation of sulforaphane and erucin metabolites in mice and cell culture

     

Synergistic cascade catalysis by metal nanoparticles and Lewis acids in hydrogen autotransfer

Of the many types of catalysis involving two or more catalysts, synergistic catalysis is of great interest because novel reactions or reaction pathways may be discovered when there is synergy between the catalysts. Herein, we describe a synergistic cascade catalysis, in which immobilized Au/Pd bimetallic nanoparticles and Lewis acids work in tandem to achieve the N-alkylation of primary amides to secondary amides with alcohols via hydrogen autotransfer. When Au/Pd nanoparticles were used with metal triflates, a significant rate acceleration was observed, and the desired secondary amides were obtained in excellent yields. The metal triflate is thought to not only facilitate the addition of primary amides to aldehydes generated in situ, but also enhance the returning of hydrogen from nanoparticles to hydrogen-accepting intermediates. This resulted in a more rapid turnover of the nanoparticle catalyst, and ultimately translated into an increase in the overall rate of the reaction. The two catalysts in this co-catalytic system work in a synergistic and cascade fashion, resulting in an efficient hydrogen autotransfer process.     

New methods to bound the critical probability in fractal percolation

We study the critical probability p_c(M) in two‐dimensional M‐adic fractal percolation. To find lower bounds, we compare fractal percolation with site percolation. Fundamentally new is the construction of a computable increasing sequence that converges to p_c(M). We prove that and . For the upper bounds, we introduce an iterative random process on a finite alphabet , which is easier to analyze than the original process. We show that and . © 2014 Wiley Periodicals, Inc. Random Struct. Alg., 47, 710–730, 2015     

Alumina aerogels prepared via rapid supercritical extraction

Alumina aerogels with surface areas from 460 to 840 m²/g and bulk densities from 0.025 to 0.079 g/cm³ were successfully fabricated using variations of an aluminum isopropoxide-based recipe developed by Armor and Carlson and the rapid supercritical extraction (RSCE) process developed at Union College. By utilizing the Union College RSCE method, it is possible to convert an alumina aerogel precursor mixture into aerogel monoliths in as little as 7.5 h. This process is safer than methanol extraction in an autoclave and faster and simpler than liquid CO₂ solvent exchange and extraction. By increasing the concentration of aqueous HNO₃ used in the precursor mixture, we were able to fabricate aerogels with significantly increased surface area, decreased bulk density, and altered microstructure. We attribute the observed variation in these aerogel properties at a given HNO₃ concentration to environmental factors such as humidity. The ability to more easily fabricate alumina aerogels with desirable properties will assist in making them a viable option for catalytic and other applications.     

Glyco‐pseudopolyrotaxanes: Carbohydrate Wheels Threaded on a Polymer String and Their Inhibition of Bacterial Adhesion

We report glyco‐pseudopolyrotaxanes composed of cucurbit[6]uril‐based mannose wheels (ManCB[6]) threaded on polyviologen (PV), which not only effectively induce bacterial aggregation, but also exhibit high inhibitory activity against bacterial binding to host cells. Three glyco‐pseudopolyrotaxanes ( 1 – 3 ), which have 10, 5, and 3 ManCB[6] wheels, respectively, on a PV string, were prepared and characterized. Bacterial aggregation assays and hemagglutination inhibition assays illustrated the specific and multivalent interaction between the glyco‐pseudopolyrotaxanes and E. coli ORN178. Compound 3 was especially effective at inducing bacterial aggregation and showed 300 times higher inhibitory potency than monomeric methyl‐α‐mannoside (Me‐αMan) for ORN178‐induced hemagglutination. Furthermore, we demonstrated their inhibitory activities for the adhesion of ORN178 bacteria to urinary epithelial cells as a model of urinary tract infection. Our findings suggest that these supramolecular carbohydrate clusters are potentially useful in antiadhesion therapy.     

Protein-peptide affinity determination using an H/D exchange dilution strategy: Application to antigen-antibody interactions

A new methodology using hydrogen/deuterium amide exchange (HDX) to determine the binding affinity of protein-peptide interactions is reported. The method, based on our previously established approach, protein ligand interaction by mass spectrometry, titration, and H/D exchange (PLIMSTEX) [J. Am. Chem. Soc. 2003, 125, 5252–5253], makes use of a dilution strategy (dPLIMSTEX) for HDX, using the mass of the peptide ligand as readout. We employed dPLIMSTEX to study the interaction of calcium-saturated calmodulin with the opioid peptide β-endorphin as a model system; the affinity results are in good agreement with those from traditional PLIMSTEX and with literature values obtained by using other methods. We show that the dPLIMSTEX method is feasible to quantify an antigen-antibody interaction involving a 3-nitrotyrosine modified peptide in complex with a monoclonal anti-nitrotyrosine antibody. A dissociation constant in the low nanomolar range was determined, and a binding stoichiometry of antibody/peptide of 1:2 was confirmed. In addition, we determined that the epitope in the binding interface contains a minimum of five amino acids. The dPLIMSTEX approach is a sensitive and powerful tool for the quantitative determination of peptide affinities with antibodies, complementary to conventional immuno-analytical techniques.