Identification of ovarian cancer metastatic miRNAs

Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.<br/

Green Medium for the Hydrolysis of 5-Cyanovaleramide

Hydrolysis of 5-cyanovaleramide (5-CVAM) in near-critical water without the addition of any catalyst has been demonstrated. The results demonstrated that the cyano group at one end of the carbon of 5-CVAM is more reactive than the amide group at the other end, under the same experimental conditions. The relations between 5-CVAM concentration and residence time revealed that hydrolysis of 5-CVAM shows second-order reaction kinetics in the investigated temperature range. The rate constants, average apparent activation energy and pre-exponential factor were evaluated according to the Arrhenius equation. Based on the experimental results, a carbon balance was calculated, and a hydrolysis reaction scheme of 5-CVAM was proposed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62148/1/771_ftp.pd

Quantifying rate enhancements for acid catalysis in CO 2 -enriched high-temperature water

Thermodynamic calculations revealed that 10 to 100-fold increases in reaction rate are obtainable with added CO 2 (0.1–1 MPa) for an acid-catalyzed reaction in high-temperature liquid water (HTW) that is first order in H + concentration. These calculations suggest that CO 2 is most effective as a rate-enhancing additive in HTW at lower temperatures (150–200°C). When compared with increased temperature as a competitive option for accelerating acid-catalyzed reactions in HTW, CO 2 addition generally carries a lower pressure penalty (and no temperature penalty) for the model acid-catalyzed reaction with activation energies of up to 35 kcal/mol. An experimental survey revealed that CO 2 addition is effective for achieving increased reaction rates for dibenzyl ether hydrolysis in HTW, but that bisphenol A cleavage, methyl benzoate hydrolysis, and o -phthalic acid decarboxylation were not significantly impacted by added CO 2 . This behavior is consistent with previous results for these reactions wherein mineral acid, rather than CO 2 , was added to lower the pH. A summary of experimental results reported for reactions in CO 2 -enriched HTW revealed that product yields of some reactions can be increased by a factor of 23 with added CO 2 . Taken collectively, these results suggest that CO 2 addition may be a practical technique for making HTW more attractive as a reaction medium for acid-catalyzed organic synthesis. © 2007 American Institute of Chemical Engineers AIChE J, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57897/1/11392_ftp.pd

AFM Imaging of RGD Presenting Synthetic Extracellular Matrix Using Gold Nanoparticles

Several high-resolution imaging techniques such as FESEM, TEM and AFM are compared with respect to their application on alginate hydrogels, a widely used polysaccharide biomaterial. A new AFM method applicable to RGD peptides covalently conjugated to alginate hydrogels is described. High-resolution images of RGD adhesion ligand distribution were obtained by labeling biotinylated RGD peptides with streptavidin-labeled gold nanoparticles. This method may broadly provide a useful tool for sECM characterization and design for tissue regeneration strategies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60236/1/469_ftp.pd

Electron‐ion Coulomb scattering and the electron Landau damping of Alfvén waves in the solar wind

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95528/1/jgra21228.pd

Synthesis reactions in high -temperature water.

Acid- and base-catalyzed reactions are prevalent in the chemical industry. Environmental concerns attributed to the use of acid/base catalysts has prompted research into more environmentally benign methods to carry out such reactions. We have explored high-temperature water (HTW) as a reaction medium that can be used without any added acid or base. We have tested high-temperature water for carbon-carbon bond forming reactions by examining the benzil-benzilic acid rearrangement and crossed aldol condensations. Additionally, we have conducted the broadest study to date of pH effects on acid and base-catalyzed reactions (primarily hydrolysis) in HTW. We investigate claims by previous researchers that acid catalysis occurs exclusively via hydronium ions from HTW in these systems. We demonstrated the feasibility of two different crossed aldol condensations in pure liquid water at temperatures of 250, 300, and 350&deg;C. We synthesized benzalacetone from benzaldehyde and acetone, and chalcone from benzaldehyde and acetophenone. We provide evidence that these reactions can be acid and base catalyzed in HTW. A reaction network with reversible formation of the unsaturated ketone, its degradation, and a path for benzaldehyde disproportion provided the basis for a quantitative reaction model. We also found that the crossed aldol condensations performed at decreasing water:organic loadings promoted higher yields. Evidence of the on-water effect was found at low water loadings with a mixer speed of 1500 rpm. Additionally the reaction was found to occur neat at 250&deg;C despite the lack of any added acid/base catalyst. The rearrangement of benzil is base (and not acid) catalyzed under conventional conditions (water-dioxane mixture around 100&deg;C). We examined this reaction in HTW between 300-380&deg;C with the intent of studying a reaction that proceeds solely by base catalysis in this more environmentally benign medium. The rearrangement proceeds in neutral HTW without addition of base, but the yield of rearrangement products is nearly insensitive to pH at near-neutral conditions. We conclude from our pH studies that the benzil rearrangement is catalyzed by acid, base, and water in HTW. The dominant mechanism shifts as the pH changes. This system shows that mechanisms that are unimportant at conventional reaction conditions can become dominant in HTW. It also demonstrates the ability to use pH to direct the selectivity of a reaction in HTW. We have also elucidated the kinetics in neutral water for both the rearrangement of benzil to benzilic acid and for the subsequent reactions of benzilic acid. The rearrangement is rapid, and the benzilic acid formed can react via two parallel pathways. The set of reaction pathways is consistent with the experimental data obtained from the reactions of benzil, diphenylacetic acid, and benzhydrol, individually, in HTW. In all of the tested reaction systems we found that specific acid/base-catalysis did not appear to be the primary mechanism in HTW at near neutral conditions. These systems included ester (methyl benzoate) and ether (methyl t-butyl ether) hydrolyses, reaction systems in which H3O+ or OH - were postulated as the catalytic agent by previous researchers.Ph.D.Applied SciencesChemical engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126390/2/3253243.pd