Design, synthesis, and evaluation of a radicicol and geldanamycin chimera, radamide

A chimera composed of the natural products radicicol and geldanamycin has been prepared through an amide linkage connecting the resorcinol moiety of radicicol to the quinone ring of geldanamycin. The inhibitory activity of these compounds was determined by their ability to inhibit Hsp90's inherent ATPase activity along with degradation of the Hsp90 client protein, HER-2 in MCF-7 breast cancer cells. [reaction: see text]     

The Predissociation of the 1(3)Sigma(-)(g) State of (7)Li(2)

The predissociation of the 1(3)Sigma(-)(g) v >/= 10 levels of (7)Li(2) has been observed by pulsed and continuous-wave perturbation-facilitated optical-optical double-resonance spectroscopy (PFOODR). Our ab initio calculation shows that the inner wall of the 1(3)Sigma(-)(g) potential intersects the 1(3)Pi(g) repulsive potential at internuclear distance R = 2.00 ?. The predissociation is due to a DeltaS = 0, DeltaLambda = +/-1 rotational-electronic interaction with the repulsive 1(3)Pi(g) state. Copyright 2001 Academic Press.     

The effects of sample preparation methods on the variability of the electrospray ionization response for model drug compounds

A post-column infusion system was developed in order to analyze suppression of electrospray ionization (ESI) tandem mass spectrometry response in the presence of endogenous plasma interferences. By enabling direct detection of these interfering components, this experimental system was used to analyze the ability of several common extraction procedures to remove endogenous plasma components that cause changes in the ESI response of model drug substances. Methyl-t-butyl ether (MTBE) liquid-liquid, Oasis and Empore solid-phase, and acetonitrile (ACN) protein precipitation sample preparation methods were tested using the post-column infusion system. In all cases, ACN protein precipitation samples showed the greatest amount of ESI response suppression while liquid-liquid extracts demonstrated the least. In addition, the three test compounds, phenacetin, caffeine, and a representative Merck compound, demonstrated that ESI response suppression is compound dependent. Suppression was greatest with caffeine, the most polar analyte, and the smallest for the Merck compound, the least polar analyte. Copyright 1999 John Wiley & Sons, Ltd.     

Gamma-ray spectroscopy with relativistic exotic heavy-ions

Feasibility of gamma-ray spectroscopy at relativistic energies with exotic heavy-ions and new generation of germanium detectors (segmented Clover) is discussed. An experiment with such detector array and radioactive is discussed.     

Percolative transport in the vicinity of charge-order ferromagnetic transition in a hole-doped manganite

We report measurements of non-linear charge transport in epitaxial (La_1−x Pr _x )_0.7Ca_0.3MnO₃ thin films fabricated on (100) oriented SrTiO₃ single crystals by pulsed laser deposition. The end members of this series, namely Pr_0.7Ca_0.3MnO₃ and La_0.7Ca_0.3MnO₃ are canonical charge-ordered (CO) and ferromagnetic manganites, respectively. The onset of the CO state in Pr_0.7Ca_0.3MnO₃ is manifested by a pronounced insulating behavior below ∼ 200 K. The CO state remains stable even when a large (∼ 2×10⁵ V/cm) electric field is applied across the thin film samples. However, on substitution of Pr with La, a crossover from the highly resistive CO state to a state of metallic character is observed at relatively low electric fields. The current-voltage characteristics of the samples at low temperatures show hysteretic and history dependent effects. The electric field driven charge transport in the system is modelled on the basis of an inhomogeneous medium consisting of ferromagnetic metallic clusters dispersed in a CO background.     

X-ray pump optical probe cross-correlation study of GaAs

Ultrafast dynamics in atomic, molecular and condensed-matter systems are increasingly being studied using optical-pump, X-ray probe techniques where subpicosecond laser pulses excite the system and X-rays detect changes in absorption spectra and local atomic structure(1-3). New opportunities are appearing as a result of improved synchrotron capabilities and the advent of X-ray free-electron lasers(4,5). These source improvements also allow for the reverse measurement: X-ray pump followed by optical probe. We describe here how an X-ray pump beam transforms a thin GaAs specimen from a strong absorber into a nearly transparent window in less than 100 ps, for laser photon energies just above the bandgap. We find the opposite effect-X-ray induced optical opacity-for photon energies just below the bandgap. This raises interesting questions about the ultrafast many-body response of semiconductors to X-ray absorption, and provides a new approach for an X-ray/optical cross-correlator for synchrotron and X-ray free-electron laser applications.     

Biotinylated geldanamycin

Inhibition of the 90 kDa heat shock proteins (Hsp90) represents a promising new chemotherapeutic approach for the treatment of several cancers. Hsp90 is essential to the survival of cancer cells and is inhibited by members of the ansamycin family of antibiotics. In particular, the quinone-containing antibiotics geldanamycin (GDA) and herbimycin A inhibit Hsp90 function in vitro at low micromolar concentrations via interaction with an ATP binding domain. Many proteins bind ATP, and the discovery of selective Hsp90 inhibitors requires the identification of other proteins that bind GDA and may cause undesired effects. Biotinylated analogues of GDA with varying tether lengths have been synthesized to elucidate other proteins that competitively bind GDA. Analogues containing a photolabile tether have also been prepared as a complementary method for the removal of GDA-bound proteins from neutravidin-containing resin. Preliminary studies indicate several proteins other than Hsp90 are isolated with biotinylated GDA.     

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Ohne Zusammenfassung     

The effect of high-dose-rate X-rays on E. coli 0157:H7 in groundbeef

The emergence of pathogens in today's world has increased the need for new, portable, nonthermal sterilization technologies. The University of Missouri, Columbia in cooperation with the Institute of Electrophysics, Ekaterinburg, Russia, have built and tested a new accelerator based on solid-state opening switches for the disinfection of pathogens in food. The accelerator utilizes a new solid-state opening switch to generate 40 ns, 2OO-keV electron beam pulses. These pulses were then converted to Bremsstrahlung X-rays using an integral X-ray converter. The efficacy of treating E. coli 0157:H7. In ground beef was tested by irradiating frozen ground beef with the high-dose-rate 10^7-6 rads/s X-ray pulses. Comparison studies were also done with a Cobalt-60 source located at the Missouri University Research Reactor. The results of the study are presented in this paper