Unusually sharp dependence of water exchange rate versus lanthanide ionic radii for a series of tetraamide complexes

The tetraamide ligand, DOTA-tetra(glycine ethyl ester), forms complexes with the lanthanide(III) cations that exist in solution predominantly as the square antiprism structure with single, slowly exchanging inner-sphere water molecule. Variable-temperature 1H and 17O NMR studies revealed that the bound water lifetimes in these complexes were sharply dependent upon the ionic radius of Ln3+ cation. A novel lanthanide-induced shift technique was used to unmask the bound water 17O resonance of SmL3+ and YL3+ complexes from the bulk water resonance. The bound water lifetime (tauM298) was approximately 800 mus in the EuL3+ complex but became much shorter (several microseconds) for Ln3+ cations with larger and smaller ionic radii. This demonstrates that water exchange is exquisitely fine-tuned in this macrocyclic tetraamide system and that a variety of Ln3+ complexes meet with the exchange requirement, Deltaomega*tauM >/= 1, necessary for an efficient MT agent.     

A Novel pH-Sensitive MRI Contrast Agent

A tetrasubstituted derivative of 1,4,7,10-tetraazacyclododecane with amide coordinating groups and extended noncoordinating phosphonate groups forms a complex with gadolinium(III) (shown in the picture) which contains one slowly exchanging inner-sphere water molecule (tau(M)=21 μs). The 20-MHz water proton relaxivity of the complex was found to be highly pH dependent. Protonation of the noncoordinating phosphonate groups appears to catalyze prototropic exchange of the bound water protons, thereby providing a mechanism for enhanced water contrast below pH 7.     

Path integral evaluation of the Eta function

In a three-dimensional model in which the gauge group does not commute with the Lorentz group, we demonstrate how the phase associated with the one-loop effective action (the function) can be computed by considering a quantum mechanical path integral.     

Comparison of combustion sources for sulfur chemiluminescence detection

Three different types of SCD combustion source have been evaluated for use in the chromatographic analysis of atmospheric sulfur compounds. The conventional FID source and the newer inverted burner source were found to be less sensitive and less stable than the flameless design. Overall, the flameless source was superior for use with HRGC-SCD.     

Transfer of hyperpolarization from long T1 storage nuclei to short T1 neighbors using FLOPSY-8

Nuclei with long T1s are optimal targets for dynamic nuclear polarization (DNP). Therefore, most of the agents used in metabolic imaging and spectroscopy studies are based on carboxylic acid moieties that lack protons, a strong source of dipolar relaxation. Metabolic flux information encoded into spectra of small molecule metabolites in the form of the 13C isotopomer data cannot be accessed using standard 13C hyperpolarization methods because protonated carbons relax too quickly through T1 dipolar relaxation. It is shown here that the longitudinal mixing sequence FLOPSY-8 can be used to transfer polarization from a long T1 storage nucleus to adjacent protonated carbons so that they may be detected with high sensitivity. We demonstrate that FLOPSY-8 allows a direct readout of isotopomer populations in butyrate and glutamate in vitro.     

Stop-like modification of the dental fricative /ð/: an acoustic analysis

This study concentrates on one of the commonly occurring phonetic variations in English: the stop-like modification of the dental fricative /e/. The variant exhibits a drastic change from the canonical /e/; the manner of articulation is changed from one that is fricative to one that is stop-like. Furthermore, the place of articulation of stop-like /e/ has been a point of uncertainty, leading to confusion between stop-like /e/ and /d/. In this study, acoustic and spectral moment measures were taken from 100 stop-like /e/ and 102 /d/ tokens produced by 59 male and 23 female speakers in the TIMIT corpus. Data analysis indicated that stop-like /e/ is significantly different from /d/ in burst amplitude, burst spectrum shape, burst peak frequency, second formant at following-vowel onset, and spectral moments. Moreover, the acoustic differences from /d/ are consistent with those expected for a dental stop-like /e/. Automatic classification experiments involving these acoustic measures suggested that they are salient in distinguishing stop-like /e/ from /d/.     

A phase I, randomized study of combined IL-2 and therapeutic immunisation with antiretroviral therapy

Background  

Fully functional HIV-1-specific CD8 and CD4 effector T-cell responses are vital to the containment of viral activity and disease progression. These responses are lacking in HIV-1-infected patients with progressive disease. We attempted to augment fully functional HIV-1-specific CD8 and CD4 effector T-cell responses in patients with advanced chronic HIV-1 infection.     

<Emphasis Type="Italic">N</Emphasis>-arachidonoyl glycine,an abundant endogenous lipid,potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor

Background  

Microglia provide continuous immune surveillance of the CNS and upon activation rapidly change phenotype to express receptors that respond to chemoattractants during CNS damage or infection. These activated microglia undergo directed migration towards affected tissue. Importantly, the molecular species of chemoattractant encountered determines if microglia respond with pro- or anti-inflammatory behaviour, yet the signaling molecules that trigger migration remain poorly understood. The endogenous cannabinoid system regulates microglial migration via CB₂ receptors and an as yet unidentified GPCR termed the 'abnormal cannabidiol' (Abn-CBD) receptor. Abn-CBD is a synthetic isomer of the phytocannabinoid cannabidiol (CBD) and is inactive at CB₁ or CB₂ receptors, but functions as a selective agonist at this G_i/o-coupled GPCR. N-arachidonoyl glycine (NAGly) is an endogenous metabolite of the endocannabinoid anandamide and acts as an efficacious agonist at GPR18. Here, we investigate the relationship between NAGly, Abn-CBD, the unidentified 'Abn-CBD' receptor, GPR18, and BV-2 microglial migration.