NMR Studies of Drugs. Applications of Achiral and Chiral Lanthanide Shift Reagents to a 5-Substituted-4-thiazolidinone

The 60 MHz ¹H NMR spectra of racemic 5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]-4-thiazolidinone, 1, have been studied in CDCl₃ solution at 28° with the achiral lanthanide shift reagent (LSR), tris (6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium (III), 2, and the chiral LSRs, tris[3-(heptafluoropropylhydroxymethylene)- (+)-camphoratojeuropium(III), 3, and tris[3-(trifluoromethylhydroxymethylene-(+) -camphorato]europium (III), 4, Significant enantiomeric shift differences were observed in the presence of added 3, for the aryl protons of 1 that should permit direct determination of enantiomeric excess. Relative magnitudes of lanthanide-induced shift for the different nuclei of 1 with the three LSRs are compared and discussed in terms of preferred LSR binding sites. A favored conformation of 1 with respect to rotation about the C(5)-CH₂ bond is suggested.     

Endolaryngeal contact pressures

In this work, we present a new method for in vivo endolaryngeal contactpressure measurement with a miniature pressure transducer. Using this methodology, contact pressures can be measured during videoendoscopy at different locations between the artyenoids and also at various locations along the membranous vocal folds. Twenty adults with organic and functional voice disorders and two vocally healthy adults participated as subjects. Endolaryngeal contact pressure measures were made during a series of phonatory tasks varying pitch, loudness, and phonatory onset and offset. Measures were also made during nonphonatory tasks, including throat clearing, coughing, Valsalva maneuvres, and gagging. The most remarkable findings were: (1) interarytenoid contact pressures were considerably greater than intraglottal contact pressures; (2) interarytenoid contact pressures were greater for lower than higher pitches; (3) both interarytenoid and intraglottal contact pressures were remarkably large during hard glottal attack; and (4) overall, the largest endolaryngeal pressures were recorded between the arytenoids, during a thoracic fixation maneuver and during gag reflex.This work was supported in part by Deutsche Forschungsgemeinschaft (He 2869/1-1), by a grant from the “Verein zur Förderung hör-, sprach- und stimmgestörter Patienten an der FU Berlin e.V.” (nonprofit organization), Berlin, Germany, and by Grant No. K08 DC00139 from the National Institute on Deafness and Other Communication Disorders.     

Anatomical location of Macrophage Migration Inhibitory Factor in urogenital tissues,peripheral ganglia and lumbosacral spinal cord of the rat

Background

Previous work suggested that macrophage migration inhibitory factor (MIF) may be involved in bladder inflammation. Therefore, the location of MIF was determined immunohistochemically in the bladder, prostate, major pelvic ganglia, sympathetic chain, the L6-S1 dorsal root ganglia (DRG) and the lumbosacral spinal cord of the rat.

Results

In the pelvic organs, MIF immunostaining was prominent in the epithelia. MIF was widely present in neurons in the MPG and the sympathetic chain. Some of those neurons also co-localized tyrosine hydroxylase (TH). In the DRGs, some of the neurons that stained for MIF also stained for Substance P. In the lumbosacral spinal cord, MIF immunostaining was observed in the white mater, the dorsal horn, the intermediolateral region and in the area around the central canal. Many cells were intensely stained for MIF and glial fibrillary acidic protein (GFAP) suggesting they were glial cells. However, some cells in the lumbosacral dorsal horn were MIF positive, GFAP negative cells suggestive of neurons.

Conclusions

Therefore, MIF, a pro-inflammatory cytokine, is localized to pelvic organs and also in neurons of the peripheral and central nervous tissues that innervate those organs. Changes in MIF's expression at the end organ and at peripheral and central nervous system sites suggest that MIF is involved in pelvic viscera inflammation and may act at several levels to promote inflammatory changes.

     

The Bonebrake Theological Seminary: Top-Secret Manhattan Project Site

We discuss the top-secret Manhattan Project site established at the Bonebrake Theological Seminary in 1943 in Dayton, Ohio, where research on polonium and its production was carried out. The polonium produced there was then transported to Los Alamos to be used in a polonium–beryllium neutron source whose purpose was to ignite the plutonium implosion bomb that would be dropped on Nagasaki, Japan, on August 9, 1945. Our account is based primarily on the recollections of John J. Sopka, research physicist at the Bonebrake laboratory.     

Limit on right handed weak coupling parameters from inelastic neutrino interactions

Right handed weak quark currents coupled to the usual left handed weak lepton current would be seen in inclusive antineutrino scattering on nuclei as a contribution at largey with the quark (not antiquark) structure function. We do not see such a term, and can therefore put an upper limit on the relative strengths of such right handed currents: \(\varrho ^2 = \frac{{\sigma _R }}{{\sigma _L }}< 0.009\) , 90% confidence. This measurement puts limits on the mixing angle of left-right symmetric models. In distinction to similar limits derived from muon decay or β decay, our limits are also valid if the right handed neutrino is heavy.     

Brans–Dicke geometry

We reveal the non-metric geometry underlying ω→0$\omega \to 0$ Brans–Dicke theory by unifying the metric and scalar field into a single geometric structure. Taking this structure seriously as the geometry to which matter universally couples, we show that the theory is fully consistent with solar system tests. This is in striking contrast with the standard metric coupling, which grossly violates post-Newtonian experimental constraints.     

Determination of 25 elements in the complex oxide mineral zirconolite by analytical electron microscopy

In this paper we describe a technique for the determination of 25 elements in natural zirconolite using energy-dispersive analytical electron microscopy (AEM). The method presented here allows one to quantitatively investigate the chemistry of submicron-scale zones in complex oxide minerals. The effects of electron channeling, thickness variability and variations in detector resolution were minimized by using a controlled set of operating procedures and instrument parameters. To provide a high level of accurayy, k_ATI-factors were determined from standards for most of the 25 elements of interest, including all of the major elements. Each analytical spectrum is reduced to a set of raw peak counts (and errors) using a digital top-hat filter to suppress background followed by multiple least squares fitting of reference spectra. Counting times of 12–15 min per analysis were required to provide suitable counting statistics. Results are presented for zirconolite samples from the contact metamorphic aureole of the Bergell granodiorite intrusion, Switzerland-Italy. A comparison of 43 AEM analyses with 15 analyses obtained by wavelength-dispersive electron probe microanalysis (EPMA) shows that there is excellent agreement between the two data sets in the amounts of individual elements present, chemical trends and overall stoichiometry. An assessment of the combined data set shows that the major substitution mechanisms in the Bergell samples are coupled substitutions involving the M5,6- and M8-sites of the zirconolite structure: ^M8Ca²⁺ + ^M5,6Ti⁴⁺→^M8REE³⁺ + ^M5,6(Al,Fe)³⁺ and ^M8Ca²⁺ + ^M5,6Ti⁴⁺→^M8(Th,U)⁴⁺ + ^M5,6 (Mg,Fe)²⁺.