Optimum excitation of “enhanced” central transition populations

Central transition (CT) sensitivity enhancement schemes that transfer polarization from satellites to the CT through selective saturation or inversion of neighboring satellite transitions have provided a welcome improvement for magic-angle spinning spectra of half-integer quadrupole nuclei. While many researchers have investigated and developed different methods of creating enhanced CT populations, here we investigate the conversion of these enhanced CT populations into observable CT coherence. We show a somewhat unexpected result that a conversion pulse length optimized for maximum sensitivity on equilibrium populations may not be optimum for an enhanced (non-equilibrium) polarization. Furthermore, CT enhancements can be lost if excessive rf field strength is used to convert this enhanced polarization into CT coherence. While a maximally enhanced CT signal is expected when using a perfectly selective CT conversion pulse, we have found that significant sensitivity loss can occur when using surprisingly low rf field strengths, even for sites with relatively large quadrupole coupling constants. We have systematically investigated these issues, and present some general guidelines and expectations when optimizing the conversion of enhanced (non-equilibrium) CT populations into observable CT coherence.     

Longitudinal changes in HIV-specific IFN-γ secretion in subjects who received Remune™ vaccination prior to treatment interruption

Background  

Despite the benefits of highly active antitretroviral therapy (HAART) for suppressing viral replication in HIV infection, virus persists and rebounds during treatment interruption (TI). This study explored whether HAART intensification with Remune™ vaccination before TI can boost HIV-1-specific immunity, leading to improved control of viremia off HAART.     

Isoflavones from Ficus nymphaefolia

A new isoflavone, 5,7-dihydroxy-4'-methoxy-3'-(2,3-dihydroxy-3-methylbutyl)isoflavone (1) was isolated from the stem bark of Ficus nymphaefolia Mill. (Moraceae) together with eight known isoflavones: genistein, erycibenin A, cajanin, 5,7,2'-trihydroxy-4'-methoxyisoflavone, erythrinin C, alpinumisoflavone, derrone and 3'-(3-methylbut-2-enyl)biochanin A. Their structures were established by spectral analysis including 1D and 2D NMR experiments.     

Deuterium kinetic isotope effects in microsolvated gas-phase E2 reactions

This work describes the first experimental studies of deuterium kinetic isotope effects (KIEs) for the gas-phase E2 reactions of microsolvated systems. The reactions of F(-)(H(2)O)(n) and OH(-)(H(2)O)(n), where n = 0, 1, with (CH(3))(3)CX (X = Cl, Br), as well as the deuterated analogs of the ionic and neutral reactants, were studied utilizing the flowing afterglow-selected ion flow tube technique. The E2 reactivity is found to decrease with solvation. Small, normal kinetic isotope effects are observed for the deuteration of the alkyl halide, while moderately inverse kinetic isotope effects are observed for the deuteration of the solvent. Minimal clustering of the product ions is observed, but there are intriguing differences in the nature and extent of the clustering process. Electronic structure calculations of the transition states provide qualitative insight into these microsolvated E2 reactions.     

The tumor inhibitor and antiangiogenic agent withaferin A targets the intermediate filament protein vimentin

The natural product withaferin A (WFA) exhibits antitumor and antiangiogenesis activity in vivo, which results from this drug's potent growth inhibitory activities. Here, we show that WFA binds to the intermediate filament (IF) protein, vimentin, by covalently modifying its cysteine residue, which is present in the highly conserved alpha-helical coiled coil 2B domain. WFA induces vimentin filaments to aggregate in vitro, an activity manifested in vivo as punctate cytoplasmic aggregates that colocalize vimentin and F-actin. WFA's potent dominant-negative effect on F-actin requires vimentin expression and induces apoptosis. Finally, we show that WFA-induced inhibition of capillary growth in a mouse model of corneal neovascularization is compromised in vimentin-deficient mice. These findings identify WFA as a chemical genetic probe of IF functions, and illuminate a potential molecular target for withanolide-based therapeutics for treating angioproliferative and malignant diseases.     

Addressing a vascular endothelium array with blood components using underlying microfluidic channels

Here, we show that an array of endothelial cells, addressable by an underlying microfluidic network of channels containing red blood cells, can be employed as an in vitro model of in vivo circulation to monitor cellular communication between different cell types in the drug discovery process.     

One-step chemical vapor growth of Ge/SiC(x)N(y) nanocables

Single-step synthesis of one-dimensional Ge/SiCxNy core-shell nanocables was achieved by chemical vapor deposition of the molecular precursor [Ge{N(SiMe3)2}2]. Single crystalline Ge nanowires (diameter approximately 60 nm) embedded in uniform SiCxNy shells were obtained in high yields, whereby the growth process was not influenced by the nature of substrates. The shell material exhibited high oxidation and chemical resistance at elevated temperatures (up to 250 degrees C) resulting in the preservation of size-dependent semiconductor properties of germanium nanowires, such as intact transport of charge carriers and reduction of energy consumption, when compared to pure Ge nanowires.     

On the structure of palau'amine: evidence for the revised relative configuration from chemical synthesis

Hexacyclic congeners 3 and 4 of palau'amine, which incorporate both guanidine functional groups and have the cis configuration of the azabicyclo[3.3.0]octane core, are prepared in 14 steps from cycloadduct 6. Synthetic access to these analogues allows the first direct comparison of NMR data for hexacyclic diguanidine structures having the originally proposed cis-azabicyclo[3.3.0]octane fragment with data for natural alkaloids of the palau'amine family. This comparison provides convincing evidence in favor of the recently proposed structural revision of these marine alkaloids, fully supporting the trans configuration of the central azabicyclo[3.3.0]octane ring system of palau'amine and congeners.