A rare earth-DOTA-binding antibody: probe properties and binding affinity across the lanthanide series

An antibody that binds rare earth complexes selectively could be used as a docking station for a set of probe molecules, of particular interest for medical imaging and therapy. The rare earths are rich in probe properties, such as the paramagnetism of Gd, the luminescence of Tb and Eu, and the nuclear properties of Lu and Y. We find that antibody 2D12.5, initially developed to bind analogues of Y-DOTA (1,4,7,10-tetraazacyclododecane-N,N',N' ',N' '-tetraacetic acid) for radiotherapy, binds not only Y-DOTA analogues but also analogous DOTA complexes of all of the lanthanides. Surprisingly, chelates of some metals such as Gd3+ bind more tightly than the original Y3+ complex. When the shape of the complex is perturbed by either increasing or decreasing the radius of the lanthanide ion, the thermodynamic stability of the protein-ligand complex changes in a regular fashion. The behavior of DeltaDeltaG as a function of ionic radius fits a parabola, as might be expected for a system that behaves in a thermodynamically elastic way. The broad specificity and high affinity of this antibody for all rare earth-DOTA complexes make it particularly interesting for applications that take advantage of the unique characteristics of lanthanides. For example, UV excitation of the Tb-DOTA-2D12.5 complex leads to energy transfer from aromatic side chains of the antibody to bound Tb-DOTA, enhancing green terbium luminescence >104 relative to unbound Tb-DOTA.     

The radiative capture of fast protons by medium-mass nuclei

High-energy photon spectra were obtained with moderate resolution for a number of neighboring nuclei: ⁵⁶Fe, ⁵⁹Co, ⁵⁸Ni, ⁶⁰Ni, ⁶¹Ni, ⁶³Cu and ⁶⁴Zn in bombardments with protons (8 to 22 MeV). The shapes, magnitudes and energy dependence of the observed spectra are found to be consistent in most of their essential features with the implications of the semidirect model for fast nucleon capture.     

A review of conventional explosives detection using active neutron interrogation

Conventional explosives are relatively easy to obtain and may cause massive harm to people and property. There are several tools employed by law enforcement to detect explosives, but these can be subverted. Active neutron interrogation is a viable alternative to those techniques, and includes: fast neutron analysis, thermal neutron analysis, pulsed fast/thermal neutron analysis, neutron elastic scatter, and fast neutron radiography. These methods vary based on neutron energy and radiation detected. A thorough review of the principles behind, advantages, and disadvantages of the different types of active neutron interrogation is presented.     

Cyclization by intramolecular carbolithiation of alkyl- and vinyllithiums prepared by the action of aromatic radical anions on phenyl thioethers. High stereoselectivity in the cyclization accelerated by an allylic lithium oxyanion

The reductive lithiation of alkyl and vinyl phenyl thioethers by aromatic radical anions is shown to be the most general method yet known for preparing organolithiums capable of intramolecular carbometalation of unactivated alkenes to produce five-membered rings and in one case a four-membered ring (in a far higher yield than known cases). The relative rates of cyclization for alkyllithiums are secondary > tertiary > primary, and the yields are very high. In the secondary case, the stereoselectivity is extremely high, producing a cyclopentylmethyllithium with a trans-2-alkyl substituent. A remarkable finding is that for all of the organolithiums a lithium oxyanionic group in the proximal allylic position to the alkene greatly accelerates the cyclization and leads almost exclusively to a trans relationship between the CH(2)Li group and the OLi group, the opposite relationship from that observed in intramolecular carbolithiations by allyllithiums. A mechanistic rationale for this divergence is discussed. One of the two types of proximal homoallylic lithium oxyanions exerts an analogous effect. An intriguing limitation, even occurring with the highly reactive secondary organolithium and in the presence of an allylic oxyanionic group, is the failure of intramolecular carbolithiation when a methyl group is at the terminus of the alkene.     

Photoacoustic spectrometer for accurate,continuous measurements of atmospheric carbon dioxide concentration

We have developed a portable photoacoustic spectrometer that offers routine, precise and accurate measurements of the molar concentration of atmospheric carbon. The temperature-controlled spectrometer continuously samples dried atmospheric air and employs an intensity-modulated distributed feedback laser and fiber amplifier operating near 1.57 µm. For measurements of carbon dioxide in air, we demonstrate a measurement precision (60-s averaging time) of 0.15 µmol mol^?1 and achieve a standard uncertainty of 0.8 µmol mol^?1 by calibrating the analyzer response in terms of certified gas mixtures. We also investigate how water vapor affects the photoacoustic signal by promoting collisional relaxation of the carbon dioxide.     

PHOTOREPAIR OF PYRIMIDINE DIMERS IN HUMAN SKIN IN VIVO

Abstract— The exposure of human skin in vivo to UV radiation emitted from a sunlamp induces the formation of pyrimidine dimers. The number of dimers, as detected by UV-endonuclease, decreases following exposure of the UV–irradiated skin to visible wavelengths of light. These results suggest that humans possess a mechanism by which pyrimidine dimers are photorepaired upon illumination of human skin in vivo with visible light.     

Autism and urinary exogenous neuropeptides: development of an on-line SPE–HPLC–tandem mass spectrometry method to test the opioid excess theory

Autism is a complex neurodevelopmental disorder with unknown etiology. One hypothesis regarding etiology in autism is the “opioid peptide excess” theory that postulates that excessive amounts of exogenous opioid-like peptides derived from dietary proteins are detectable in urine and that these compounds may be pathophysiologically important in autism. A selective LC–MS/MS method was developed to analyze gliadinomorphin, β-casomorphin, deltorphin 1, and deltorphin 2 in urine. The method is based on on-line SPE extraction of the neuropeptides from urine, column switching, and subsequent HPLC analysis. A limit of detection of 0.25 ng/mL was achieved for all analytes. Analyte recovery rates from urine ranged between 78% and 94%, with relative standard deviations of 0.2–6.8%. The method was used to screen 69 urine samples from children with and without autism spectrum disorders for the occurrence of neuropeptides. The target neuropeptides were not detected above the detection limit in either sample set. Dedicated to Prof. Werner Engewald on the occasion of his 70th birthday.