Identification of Toxin Inhibitors Using a Magnetic Nanosensor‐Based Assay

A magnetic nanosensor‐based method is described to screen a library of drugs for potential binding to toxins. Screening is performed by measuring changes in the magnetic relaxation signal of the nanosensors (bMR nanosensors) in aqueous suspension upon addition of the toxin. The Anthrax lethal factor (ALF) is selected as a model toxin to test the ability of our bMR nanosensor‐based screening method to identify potential inhibitors of the toxin. Out of 30 molecules screened, sulindac, naproxen and fusaric acid are found to bind LF, with dissociation constants in the low micromolar range. Further biological analysis of the free molecules in solution indicate that sulindac and its metabolic products inhibited LF cytotoxicity to macrophages with IC₅₀ values in the micromolar range. Meanwhile, fusaric acid is found to be less effective at inhibiting LF cytotoxicity, while naproxen does not inhibit LF toxicity. Most importantly, when the sulindac and fusaric acid‐bMR nanosensors themselves are tested as LF inhibitors, as opposed to the corresponding free molecules, they are stronger inhibitors of LF with IC₅₀ values in the nanomolar range. Taken together, these studies show that a bMR nanosensors‐based assay can be used to screen known drugs and other small molecules for inhibitor of toxins. The method can be easily modified to screen for inhibitors of other molecular interactions and not only the selected free molecule can be study as potential inhibitors but also the bMR nanosensors themselves achieving greater inhibitory potential.     

Concave utility, transaction costs, and risk in measuring discounting of delayed rewards.

Research has consistently found that the decline in the present values of delayed rewards as delay increases is better fit by hyperbolic than by exponential delay-discounting functions. However, concave utility, transaction costs, and risk each could produce hyperbolic-looking data, even when the underlying discounting function is exponential. In Experiments 1 (N=45) and 2 (N=103), participants placed bids indicating their present values of real future monetary rewards in computer-based 2nd-price auctions. Both experiments suggest that utility is not sufficiently concave to account for the superior fit of hyperbolic functions. Experiment 2 provided no evidence that the effects of transaction costs and risk are large enough to account for the superior fit of hyperbolic functions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Magnetic resonance compatibility of multichannel silicon microelectrode systems for neural recording and stimulation: design criteria, tests, and recommendations

Magnetic resonance (MR) compatibility of biomedical implants and devices represents a challenge for designers and potential risks for users. This paper addresses these problems and presents the first MR-compatible multichannel silicon chronic microelectrode system, used for recording and electrical stimulation of the central nervous system for animal models. A standard chronic assembly, from the Center for Neural Communication Technology at the University of Michigan, was tested on a 2 Tesla magnet to detect forces, heating, and image distortions, and modified to minimize or eliminate susceptibility artifacts, tissue damage, and electrode displacement, maintaining good image quality and safety to the animals. Multiple commercial connectors were tested for MR compatibility and several options for the reference electrode were also tested to minimize image artifacts and provide a stable biocompatible reference for shortand long-term neural recordings. Different holding screws were tested to anchor the microelectrode assembly on the top of the skull. The final selection of this part was based on MR-compatibility, biocompatibility, durability, and mechanical and chemical stability. The required adaptor to interconnect the MR-compatible microelectrode with standard data acquisition systems was also designed and fabricated. The final design is fully MR-compatible and has been successfully tested on guinea pigs.     

Color-coded perfluorocarbon nanodroplets for multiplexed ultrasound and photoacoustic imaging

Laser-activated perfluorocarbon nanodroplets are an emerging class of phase-change, dual-contrast agents that can be utilized in ultrasound and photoacoustic imaging. Through the ability to differentiate subpopulations of nanodroplets via laser activation at different wavelengths of near-infrared light, optically-triggered color-coded perfluorocarbon nanodroplets present themselves as an attractive tool for multiplexed ultrasound and photoacoustic imaging. In particular, laser-activated droplets can be used to provide quantitative spatiotemporal information regarding distinct biological targets, allowing for their potential use in a wide range of diagnostic and therapeutic applications. In the work presented, laser-activated color-coded perfluorocarbon nanodroplets are synthesized to selectively respond to laser irradiation at corresponding wavelengths. The dynamic ultrasound and photoacoustic signals produced by laser-activated perfluorocarbon nanodroplets are evaluated in situ prior to implementation in a murine model. In vivo, these particles are used to distinguish unique particle trafficking mechanisms and are shown to provide ultrasound and photoacoustic contrast for up to 72 hours within lymphatics. Overall, the conducted studies show that laser-activated color-coded perfluorocarbon nanodroplets are a promising agent for multiplexed ultrasound and photoacoustic imaging.

     

Carbon Nanotubes Prepared by Catalytic Decomposition of Benzene Over Silica Supported Cobalt Catalysts

Carbon nanostructures were prepared by catalytic decomposition of benzene on Co/SiO₂ catalysts at 873 K. As a function of particle size and reactive mixture, carbon filaments and nanotubes were obtained and various shapes observed such as straight, curved and helically-coiled nanotubes. Particularly, it was shown that the helically-coiled nanotubes do not present an ordered atomic structure as it was predicted theoretically. However, the active catalytic particle as well as the reactive environment may play an important role in the growth of such nanostructures.     

The Characterization of Tungsten-Oxide-Modified Zirconia Supports for Dual Functional Catalysis

The results of catalytic titration measurements indicated that WO _x /ZrO₂ catalysts prepared by coprecipitation have higher acid site density and strength, and are more active for pentane isomerization, than catalysts prepared by impregnation. The coprecipitated WO _x /ZrO₂ contains 0.004 meq-H⁺/g-catalyst. XPS of chemisorbed 2,6-dimethylpyridine and pyridine revealed the presence of Lewis acid sites as well as strong and weak Brønsted acid sites on the surface of these catalysts. The concentration of strong Brønsted sites was close to the concentration of Lewis sites, suggesting that the high acidity of these materials may originate from a conjugate Brønsted–Lewis site. Pt/WO _x /ZrO₂ undergoes a reversible loss of hydrogen chemisorption capacity with increasing hydrogen pretreatment temperature, accompanied by a reversible loss of pentane isomerization activity. This loss can be attributed to a strong Pt-reduced tungsten oxo species interaction (SMSI). Room temperature hydrogen spillover is observed in the Pt/WO _x /ZrO₂ (16% W) catalyst, consistent with the presence of bulk WO₃ in this material as observed by TPR.     

Evaporated cadmium telluride films on steel foil substrates

Adherent CdTe films were vacuum-evaporated on steel foil substrates heated to between 240 C and 320 C. As-deposited films were p-type and had a preferred (111) orientation with an average grain size of 0.6 m. To control the electrical properties of the films, gold or tellurium interlayers were deposited between the steel and the CdTe. A tellurium interlayer caused larger as-deposited grains than either the gold or bare steel. Annealing of CdTe films at 550 C increased the grain size and tended to transform p-type CdTe into n-type. X-ray fluorescence analysis indicated that annealing had caused iron to diffuse into the CdTe, which may have caused the type reversion.     

Effect of tilt angle variations in a halo implant on V/sub th/ values for 0.14-/spl mu/m CMOS devices

Sensitivity of critical transistor parameters to halo implant tilt angle for 0.14-/spl mu/m CMOS devices was investigated. V/sub th/ sensitivity was found to be 3% per tilt degree. A tilt angle mismatch between two serial ion implanters used in manufacturing was detected by tracking V/sub th/ performance for 0.14-/spl mu/m production lots. Even though individual implanters may be within tool specifications for tilt angle control (/spl plusmn/0.5/spl deg/ for our specific tool type), the relative mismatch could be as large as 1/spl deg/, and therefore, result in a V/sub th/ mismatch of over 3% from nominal. The V/sub th/ mismatch results are in qualitative agreement with simulation results using SUPREM and MEDICI software.     

Tyrosinase and peroxidase production by Rhizopus oryzae strain ENHE obtained from pentachlorophenol‐contaminated soil

BACKGROUND: The aim of this study was to investigate the ability of a zygomycete isolated from pentachlorophenol (PCP)‐contaminated soil to produce peroxidase and phenoloxidase enzymes, and to determine the effect of tyrosine and PCP on the enzyme activities. The ability of the isolate to tolerate and remove PCP was also studied. RESULTS: A zygomycete capable of tolerating and removing PCP was isolated from contaminated soil and identified by molecular techniques as Rhizopus oryzae strain ENHE. This fungus produced extra‐ and intracellular tyrosinase and extracellular lignin peroxidase. Tyrosinase activity increased with 0.1 g tyrosine L^?1 added to the culture medium. PCP had no effect on tyrosinase activity but increased lignin peroxidase activity. It was shown that R. oryzae ENHE grew until 100 mg PCP L^?1 and removed 90% of the initial PCP concentration of 12.5 mg L^?1 in 24 h and that the enzymes tyrosinase and lignin peroxidase were probably involved in the PCP removal process. CONCLUSION: The results indicate that R. oryzae ENHE has the potential to be used to produce tyrosinase and lignin peroxidase enzymes. In the few studies that report the production of peroxidase and extracellular tyrosinase by fungi, these enzymes are produced mainly by basidiomycetes. Copyright © 2008 Society of Chemical Industry