Structure-function analysis of the cloned opiate receptors: peptide and small molecule interactions

Opiate receptors mediate the physiological actions of opioid peptides and the clinical effects of the synthetic opioid agonists and antagonists. Site-directed mutagenesis studies have revealed regions of opiate receptors that are essential for ligand recognition, and this could aid the design of more selective opioid ligands.     

A dynamic study of earthworm feeding ecology -using stable isotopes

Changes in the specific diet of earthworms with time in relation to landuse changes and two different climates were studied by analysing (13)C and (15)N natural abundance in soils and animals. Soil samples from three depths (0-10, 10-20 and 20-30 cm) and earthworms were collected from two sites: Santiago (Northwest Spain) and North Wyke (Southwest England) both consisting of replicated long-term grasslands and recently converted to maize plots. Earthworms were hand-sorted in the field at the peak of the maize growth and after harvesting at both sites. In the Spanish plots, nine and eight earthworm species, all belonging to the three ecological categories (epigeic, anecic and endogeic), were found under maize and permanent pasture, whereas at the English site five and seven different species were, respectively, identified. At both sites (13)C isotopic values of the earthworm tissues reflected changes in diet from C(3) to C(4) with epigeic and epi/anecic worms in the maize plots showing one delta unit difference in relation to the ones found in the grassland plots. Anecic worms seemed to be less responsive to landuse changes. The higher (13)C values of the Spanish soils were also reflected in the earthworm tissues when compared with the English samples. (15)N values showed no clear relationship with the cropping treatments but were clearly related to the ecological grouping, with endogeic worms reaching the highest values whereas for the epigeic and epi/anecic species the lowest values were obtained. This finding was also previously recorded by other authors1 and suggests that, in the future, stable isotope techniques could also be a useful tool in taxonomic studies. Copyright 1999 John Wiley & Sons, Ltd.     

Secondary ion yields produced by keV atomic and polyatomic ion impacts on a self-assembled monolayer surface

A suite of keV polyatomic or 'cluster' projectiles was used to bombard unoxidized and oxidized self-assembled monolayer surfaces. Negative secondary ion yields, collected at the limit of single ion impacts, were measured and compared for both molecular and fragment ions. In contrast to targets that are orders of magnitude thicker than the penetration range of the primary ions, secondary ion yields from polyatomic projectile impacts on self-assembled monolayers show little to no enhancement when compared with monatomic projectiles at the same velocity. This unusual trend is most likely due to the structural arrangement and bonding characteristics of the monolayer molecules with the Au(111). Copyright 1999 John Wiley & Sons, Ltd.     

Quantitative single point imaging with compressed sensing

A novel approach with respect to single point imaging (SPI), compressed sensing, is presented here that is shown to significantly reduce the loss of accuracy of reconstructed images from under-sampled acquisition data. SPI complements compressed sensing extremely well as it allows unconstrained selection of sampling trajectories. Dynamic processes featuring short NMR signal can thus be more rapidly imaged, in our case the absorption of moisture by a cereal-based wafer material, with minimal loss of image quantification. The absolute moisture content distribution is recovered via a series of images acquired with variable phase encoding times allowing extrapolation to time zero for each image pixel and the effective removal of contrast.     

Study of the peak effect phenomenon in single crystals of 2H-NbSe2

The weakly pinned single crystals of the hexagonal 2H-NbSe₂ compound have emerged as prototypes for determining and characterizing the phase boundaries of the possible order-disorder transformations in the vortex matter. We present here a status report based on the ac and dc magnetization measurements of the peak effect phenomenon in three crystals of 2H-NbSe₂, in which the critical current densities vary over two orders of magnitude. We sketch the generic vortex phase diagram of a weakly pinned superconductor, which also utilizes theoretical proposals. We also establish the connection between the metastability effects and pinning.     

A Non-Analytic Growth Bound for Laplace Transforms and Semigroups of Operators

Let f : \mathbbR₊ ? \mathbbC f : \mathbb{R}_{+} \longrightarrow \mathbb{C} be an exponentially bounded, measurable function. We introduce a growth bound z(f) \zeta(f) which measures the extent to which f f can be approximated by holomorphic functions. This growth bound is related to the location of the domain of holomorphy of the Laplace transform of f f far from the real axis. The denition extends to vector and operator-valued cases. For a C₀ C_{0} -semigroup T T of operators, z(T) \zeta(T) is closely related to the critical growth bound of T T .     

Ultrahigh pressure equation of state of tantalum to 310 GPa

ABSTRACT

The isothermal compression of transition metal tantalum (Ta) was studied in a diamond anvil cell by X-ray diffraction utilizing rhenium (Re) and gold (Au) as internal X-ray pressure standards. The Re pressure marker was employed during non-hydrostatic compression to pressures up to 310?GPa while the Au pressure marker was used during quasi-hydrostatic compression in a neon pressure-transmitting medium to 80?GPa. Two ultra-high pressure experiments were conducted on Ta and Re mixtures utilizing focused-ion beam machined toroidal diamond anvils with central flats varying from 8 microns to 16 microns in diameter. The Ta metal was observed to be stable in the body-centered-cubic phase to a volume compression V/V₀?=?0.581. The measured equations of state (EOS) of Ta using two different calibrations of the Re pressure marker are compared with the ambient temperature isotherm derived from shock compression data. We provide a detailed analysis of EOS fit parameters for Ta under quasi-hydrostatic and non-hydrostatic conditions.     

Magnesium amido N-heterocyclic carbene complexes

Magnesium dications bind strongly to a tridentate anionic dicarbene ligand L = [N{CH(2)CH(2)(CNCHCHNMes)}(2)] forming dinuclear and trinuclear Mg complexes with some particularly short Mg-C bonds. Treatment of the proligand H(4)LCl(3) with three equivalents of methyl magnesium chloride or benzyl magnesium chloride affords Mg(3)(HL)Cl(6) in high yield. A suspension of in thf was heated to 80 degrees C for 2 h to afford Mg(2)(L)Cl(3), consistent with the loss of one equivalent of MgCl(2), and the deprotonation of the remaining acidic NH, lost as HCl gas. Treatment of Mg(3)(HL)Cl(6) with one equivalent of KC(8) results in deprotonation of the ligand amine NH to afford Mg(3)(L)Cl(5); treatment with a second equivalent forms the radical anion of the complex, K[Mg(3)(L)Cl(5)], which decomposes upon storage, precluding its structural characterisation. The acidic NH proton of the ligand in Mg(3)(HL)Cl(6) can also be removed by deprotonation with Li{N(SiMe(3))(2)}; additional equivalents of which also exchange the magnesium-bound chlorides for silylamido ligands, affording Mg(2)(L)Cl(2)N' and Mg(2)(L)Cl(N')(2), which have both been characterised by single-crystal X-ray diffraction studies.     

Synthetic mimics of mammalian cell surface receptors: prosthetic molecules that augment living cells

Specific receptors on the surface of mammalian cells actively internalize cell-impermeable ligands by receptor-mediated endocytosis. To mimic these internalizing receptors, my laboratory is studying artificial cell surface receptors that comprise N-alkyl derivatives of 3beta-cholesterylamine linked to motifs that bind cell-impermeable ligands. When added to living mammalian cells, these synthetic receptors insert into cellular plasma membranes, project ligand-binding small molecules or peptides from the cell surface, and enable living cells to internalize targeted proteins and other cell-impermeable compounds. These artificial receptors mimic their natural counterparts by rapidly cycling between plasma membranes and intracellular endosomes, associating with proposed cholesterol and sphingolipid-rich lipid raft membrane microdomains, and delivering ligands to late endosomes/lysosomes. This "synthetic receptor targeting" strategy is briefly reviewed here and contrasted with other related cellular delivery systems. Potential applications of artificial cell surface receptors as molecular probes, agents for cellular targeting, tools for drug delivery, and methods for ligand depletion are discussed. The construction of synthetic receptors as prosthetic molecules, designed to seamlessly augment the molecular machinery of living cells, represents an exciting new frontier in the fields of bioorganic chemistry and chemical biology.