Matrix elements of U(2n) generators in a multishell spin-orbit basis. I. The del-operator MEs in a two-shell composite Gelfand-Paldus basis

This is the first in a series of three articles which aimed to derive the matrix elements of the U(2n) generators in a multishell spin-orbit basis. This is a basis appropriate to many-electron systems which have a natural partitioning of the orbital space and where also spin-dependent terms are included in the Hamiltonian. The method is based on a new spin-dependent unitary group approach to the many-electron correlation problem due to Gould and Paldus [M. D. Gould and J. Paldus, J. Chem. Phys. 92, 7394, (1990)]. In this approach, the matrix elements of the U(2n) generators in the U(n) x U(2)-adapted electronic Gelfand basis are determined by the matrix elements of a single Ll(n) adjoint tensor operator called the del-operator, denoted by Delta(j)(i) (1 less than or equal to i, j less than or equal to n). Delta or del is a polynomial of degree two in the U(n) matrix E = [E-j(i)]. The approach of Gould and Paldus is based on the transformation properties of the U(2n) generators as an adjoint tensor operator of U(n) x U(2) and application of the Wigner-Eckart theorem. Hence, to generalize this approach, we need to obtain formulas for the complete set of adjoint coupling coefficients for the two-shell composite Gelfand-Paldus basis. The nonzero shift coefficients are uniquely determined and may he evaluated by the methods of Gould et al. [see the above reference]. In this article, we define zero-shift adjoint coupling coefficients for the two-shell composite Gelfand-Paldus basis which are appropriate to the many-electron problem. By definition, these are proportional to the corresponding two-shell del-operator matrix elements, and it is shown that the Racah factorization lemma applies. Formulas for these coefficients are then obtained by application of the Racah factorization lemma. The zero-shift adjoint reduced Wigner coefficients required for this procedure are evaluated first. All these coefficients are needed later for the multishell case, which leads directly to the two-shell del-operator matrix elements. Finally, we discuss an application to charge and spin densities in a two-shell molecular system. (C) 1998 John Wiley & Sons.

Matrix elements of U(2n) generators in a multishell spin-orbit basis. III. General formulas

This is the third and final article in a series directed toward the evaluation of the U(2n) generator matrix elements (MEs) in a multishell spin/orbit basis. Such a basis is required for many-electron systems possessing a partitioned orbital space and where spin-dependence is important. The approach taken is based on the transformation properties of the U(2n) generators as an adjoint tensor operator of U(n) x U(2) and application of the Wigner-Eckart theorem. A complete set of adjoint coupling coefficients for the two-shell composite Gelfand-Paldus basis (which is appropriate to the many-electron problem) were obtained in the first and second articles of this series. Ln the first article we defined zero-shift coupling coefficients. These are proportional to the corresponding two-shell del-operator matrix elements. See P. J. Burton and and M. D. Gould, J. Chem. Phys., 104, 5112 (1996), for a discussion of the del-operator and its properties. Ln the second article of the series, the nonzero shift coupling coefficients were derived. Having obtained all the necessary coefficients, we now apply the formalism developed above to obtain the U(2n) generator MEs in a multishell spin-orbit basis. The methods used are based on the work of Gould et al. (see the above reference). (C) 1998 John Wiley & Sons, Inc.

Delayed postural contraction of transversus abdominis in low back pain associated with movement of the lower limb

The temporal parameters of the response of the trunk muscles associated with movement of the lower limb were investigated in people with and without low back pain (LBP). The weight shift component of the task was completed voluntarily prior to a stimulus to move to allow investigation of the movement component of the response. In the control subjects the onset of electromyographic (EMG) activity of all trunk muscles preceded that of the muscle responsible for limb movement, thus contributing to the feed forward postural response. The EMG onset of transversus abdominis was delayed in the LBP subjects with movement in each direction, while the EMG onsets of rectus abdominis, erector spinae, and oblique abdominal muscles were delayed with specific movement directions. This result provides evidence of a change in the postural control of the trunk in people with LBP.

Calcium is essential for the structural integrity of the cysteine-rich, ligand-binding repeat of the low-density lipoprotein receptor

Seven cysteine-rich repeats form the ligand-binding region of the low-density lipoprotein (LDL) receptor. Each of these repeats is assumed to bind a calcium ion, which is needed for association of the receptor with its ligands, LDL and beta-VLDL. The effects of metal ions on the folding of the reduced N-terminal cysteine-rich repeat have been examined by using reverse-phase high-performance liquid chromatography to follow the formation of fully oxidized isomers with different disulfide connectivities. in the absence of calcium many of the 15 possible isomers formed on oxidation, whereas in its presence the predominant product at equilibrium had the native disulfide bond connectivities. Other metals were far less effective at directing disulfide bond formation: Mn2+ partly mimicked the action of Ca2+, but Ba2+, Sr2+, and Mg2+ had little effect. This metal-ion specificity was also observed in two-dimensional H-1 NMR spectral studies: only Ca2+ induced the native three-dimensional fold. The two paramagnetic ions, Gd3+ and Mn2+, and Cd2+ did not promote adoption of a well-defined structure, and the two paramagnetic ions did not displace calcium ions. The location of calcium ion binding sites in the repeat was also explored by NMR spectroscopy. The absence of chemical shift changes for the side chain proton resonances of Asp26, Asp36, and Glu37 from pH 3.9 to 6.8 in the presence of calcium ions and their proximal location in the NMR structures implicated these side chains as calcium ligands. Deuterium exchange NMR experiments also revealed a network of hydrogen bonds that stabilizes the putative calcium-binding loop.

Sensitive detection of nitric oxide using seeded parametric four-wave mixing

A sensitive near-resonant four-wave mixing technique based on two-photon parametric four-wave mixing has been developed. Seeded parametric four-wave mixing requires only a single laser as an additional phase matched seeder field is generated via parametric four-wave mixing of the pump beam in a high gain cell. The seeder field travels collinearly with the pump beam providing efficient nondegenerate four-wave mixing in a second medium. This simple arrangement facilitates the detection of complex molecular spectra by simply scanning the pump laser. Seeded parametric four-wave mixing is demonstrated in both a low pressure cell and an air/acetylene flame with detection of the two-photon C (2) Pi(upsilon'=0)<--X (2) Pi(upsilon =0) spectrum of nitric oxide. From the cell data a detection limit of 10(12) molecules/cm(3) is established. A theoretical model of seeded parametric four-wave mixing is developed from existing parametric four-wave mixing theory. The addition of the seeder field significantly modifies the parametric four-wave mixing behaviour such that in the small signal regime, the signal intensity can readily be made to scale as the cube of the laser pump power while the density dependence follows a more familiar square law dependence, In general, we find excellent agreement between theory and experiment. Limitations to the process result from an ac Stark shift of the two-photon resonance in the high pressure seeder cell caused by the generation of a strong seeder field, as well as a reduction in phase matching efficiency due to the presence of certain buffer species. Various optimizations are suggested which should overcome these limitations, providing even greater detection sensitivity. (C) 1998 American Institute of Physics, [S0021-9606(98)01014-9].

Book review of Mark McGillivray and Gary Smith's (eds.) "Australia and Asia", Melbourne: Oxford University Press, 1997. vii + 248 pp

The political capital invested in Australia's engagement with Asia over the past decade has sparked a lively discussion in the Australian academic community. The back cover of the book under review suggests that there are 'few bigger contemporary issues facing Australia than its relationship with Asia'. If the volume of scholarly material being produced on this issue is any indication, they are right. Like a number of similar works covering the shift in Australian foreign, defence, and trade policies towards Asia over the last decade, this book acknowledges a particular debt of gratitude to the Keating government for establishing regional engagement at the forefront of our national consciousness. Unlike some others however, this book seeks to place Australia's more recent 'discovery' of Asia into a broader historical framework.

Iron(III) and iron(II) complexes of 1-thia-4,7-diazacyclononane ([9]aneN(2)S) and 1,4-dithia-7-azacyclononane ([9]aneNS(2)). X-Ray structural analyses, magnetic susceptibility, Mossbauer, EPR and electronic spectroscopy

The complexes [Fe([9]aneN(2)S)(2)][ClO4](2), [Fe([9]aneN(2)S)(2)][ClO4](3) and [Fe([9]aneNS(2))(2)][ClO4](2) ([9]aneN(2)S = 1-thia-4. 7-diazacyclononane and [9]aneNS(2) = 1,4-dithia-7-azacyclononane) have been prepared and the latter two characterised by X-ray crystallography. The Mossbauer spectra (isomer shift/mm s(-1), quadrupole splitting/mm s(-1), 4.2 K) for [Fe([9]aneN(2)S)(2)][ClO4](2) (0.52, 0.57), [Fe([9]aneN(2)S)(2)][ClO4](3) (0.25, 2.72) and [Fe([9]aneNS(2))(2)][ClO4](2) (0.43, 0.28) are typical for iron(II) and iron(III) complexes. Variable-temperature susceptibility measurements for [Fe([9]aneN(2)S)(2)][ClO4](2) (2-300 K) revealed temperature-dependent behaviour in both the solid state [2.95 mu(B) (300 K)-0.5 mu(B) (4.2 K)] and solution (Delta H degrees 20-22 kJ mol(-1), Delta S degrees 53-60 J mol(-1) K-1). For [Fe([9]aneN(2)S)(2)][ClO4](3) in the solid state [2.3 mu(B) (300 K)-1.9 mu(B) (4.2 K)] the magnetic data were fit to a simple model (H = -lambda L . S + mu L-z) to give the spin-orbit coupling constant (lambda) of -260 +/- 10 cm(-1). The solid-state X-band EPR spectrum of [Fe([9]aneN(2)S)(2)][ClO4](3) revealed axial symmetry (g(perpendicular to) = 2.607, g(parallel to) = 1.599). Resolution of g(perpendicular to) into two components at Q-band frequencies indicated a rhombic distortion. The low-temperature single-crystal absorption spectra of [Fe([9]aneN(2)S)(2)][ClO4](2) and [Fe([9]aneNS(2))(2)][ClO4](2) exhibited additional bands which resembled pseudotetragonal low-symmetry splitting of the parent octahedral (1)A(1g) --> T-1(2g) and (1)A(1g) ---> T-1(1g) transitions. However, the magnitude of these splittings was too large, requiring 10Dq for the thioether donors to be significantly larger than for the amine donors. Instead, these bands were tentatively assigned to weak, low-energy S --> Fe-II charge-transfer transitions. Above 200 K, thermal occupation of the high-spin T-5(2g) ground state resulted in observation of the T-5(2g) --> E-5(g) transition in the crystal spectrum of [Fe([9]aneN(2)S)(2)][ClO4](2). From a temperature-dependence study, the separation of the low-spin (1)A(1g) and high-spin T-5(2g) ground states was approximately 1700 cm(-1). The spectrum of the iron(III) complex [Fe([9]aneN(2)S)(2)][ClO4](3) is consistent with a low-spin d(5) configuration.

Small molecular probes for G-protein-coupled C5a receptors: Conformationally constrained antagonists derived from the C terminus of the human plasma protein C5a

Activation of the human complement system of plasma proteins in response to infection or injury produces a 4-helix bundle glycoprotein (74 amino acids) known as C5a. C5a binds to G-protein-coupled receptors on cell surfaces triggering receptor-ligand internalization, signal transduction, and powerful inflammatory responses. Since excessive levels of C5a are associated with autoimmune and chronic inflammatory disorders, inhibitors of receptor activation may have therapeutic potential. We now report solution structures and receptor-binding and antagonist activities for some of the first small molecule antagonists of C5a derived from its hexapeptide C terminus. The antagonist NMe-Phe-Lys-Pro-D-Cha-Trp-D-Arg-CO2H (1) surprisingly shows an unusually well-defined solution structure as determined by H-1 NMR spectroscopy. This is one of the smallest acyclic peptides found to possess a defined solution conformation, which can be explained by the constraining role of intramolecular hydrogen bonding. NOE and coupling constant data, slow deuterium exchange, and a low dependence on temperature for the chemical shift of the D-Cha-NH strongly indicate an inverse gamma turn stabilized by a D-Cha-NH ... OC-Lys hydrogen bond. Smaller conformational populations are associated with a hydrogen bond between Trp-NH ... OC-Lys, defining a type II beta turn distorted by the inverse gamma turn incorporated within it. An excellent correlation between receptor-affinity and antagonist activity is indicated for a limited set of synthetic peptides. Conversion of the C-terminal carboxylate of 1 to an amide decreases antagonist potency 5-fold, but potency is increased up to 10-fold over 1 if the amide bond is made between the C-terminal carboxylate and a Lys/Orn side chain to form a cyclic analogue. The solution structure of cycle 6 also shows gamma and beta turns; however, the latter occurs in a different position, and there are clear conformational changes in 6 vs 1 that result in enhanced activity. These results indicate that potent C5a antagonists can be developed by targeting site 2 alone of the C5a receptor and define a novel pharmacophore for developing powerful receptor probes or drug candidates.

Homodyne measurements on a Bose-Einstein condensate

We investigate a nondestructive measurement technique to monitor Josephson-like oscillations between two spatially separated neutral atom Bose-Einstein condensates. One condensate is placed in an optical cavity, which is strongly driven by a coherent optical field. The cavity output field is monitored using a homodyne detection scheme. The cavity field is well detuned from an atomic resonance, and experiences a dispersive phase shift proportional to the number of atoms in the cavity. The detected current is modulated by the coherent tunneling oscillations of the condensate. Even when there is an equal number of atoms in each well initially, a phase is established by the measurement process and Josephson-like oscillations develop due to measurement backaction noise alone.

N-mesityl-C-acylketenimines: 1,5-sigmatropic shifts and electrocyclization to quinolines

Flash vacuum thermolysis (FVT) of triazoles 6a-c generates alpha-oxoketenimines 10, the ester 10a being isolable. FVT of pyrroledione 8 generates the isomeric imidoylketene 9a. Ketenes 9 and ketenimines 10 undergo thermal interconversion by 1,3-shifts of methoxy and dimethylamino groups under mild FVT conditions (ca. 350-400 degrees C). Both 9 and 10 are directly observable by IR spectroscopy at either 77 K or on Ar matrix isolation at 12 K. On FVT at temperatures above ca. 400 degrees C, the ketenimines 10 undergo a 1,5-H shift to o-quinoid imines 12/13, followed by electrocyclization to dihydroquinolines 14 (unobserved) and 15 (observed by NMR). The latter are easily oxidized to alkylquinoline-3-carboxylates or quinoline-3-carboxamides 16 by atmospheric oxygen. Ab initio calculations on model compounds 18-23 predict an energy barrier of ca. 38 kcal mol(-1) (161 kJ mol(-1)) for the 1,5-H shift in N-(o-methylphenyl)ketenimines via the transition state TS19 followed by an electrocyclization barrier to dihydroquinoline 23a via TS22a of ca. 16 kcal mol(-1).

Solution structure of methionine-oxidized amyloid beta-peptide (1-40). Does oxidation affect conformational switching?

The solution structure of A beta(1-40)Met(O), the methionine-oxidized form of amyloid beta-peptide A beta(1-40), has been investigated by CD and NMR spectroscopy. Oxidation of Met35 may have implications in the aetiology of Alzheimer's disease. Circular dichroism experiments showed that whereas A beta(1-40) and A beta(1-40)Met(O) both adopt essentially random coil structures in water (pH 4) at micromolar concentrations, the former aggregates within several days while the latter is stable for at least 7 days under these conditions. This remarkable difference led us to determine the solution structure of A beta(1-40)Met(O) using H-1 NMR spectroscopy. In a water-SDS micelle medium needed to solubilize both peptides at the millimolar concentrations required to measure NMR spectra, chemical shift and NOE data for A beta(1-40)Met(O) strongly suggest the presence of a helical region between residues 16 and 24. This is supported by slow H-D exchange of amide protons in this region and by structure calculations using simulated annealing with the program XPLOR. The remainder of the structure is relatively disordered. Our previously reported NMR data for A beta(1-40) in the same solvent shows that helices are present over residues 15-24 (helix 1) and 28-36 (helix 2), Oxidation of Met35 thus causes a local and selective disruption of helix 2. In addition to this helix-coil rearrangement in aqueous micelles, the CD data show that oxidation inhibits a coil-to-beta-sheet transition in water. These significant structural rearrangements in the C-terminal region of A beta may be important clues to the chemistry and biology of A beta(1-40) and A beta(1-42).

Structure-activity studies of conantokins as human N-methyl-D-aspartate receptor modulators

The activities of conantokin-G (con-G), conantokin-T (con-T), and several novel analogues have been studied using polyamine enhancement of [H-3]MK-801 binding to human glutamate-N-methyl-D-aspartate (NMDA) receptors, and their structures have been examined using CD and H-1 NMR spectroscopy. The potencies of con-G[A7], con-G, and con-T as noncompetitive inhibitors of spermine-enhanced [H-3]MK-801 binding to NMDA receptor obtained from human brain tissue are similar to those obtained using rat brain tissue. The secondary structure and activity of con-G are found to be highly sensitive to amino acid substitution and modification. NMR chemical shift data indicate that con-G, con-G[D8,D17], and con-G[A7] have similar conformations in the presence of Ca2+. This consists of a helix for residues 2-16, which is kinked in the vicinity of Gla10. This is confirmed by 3D structure calculations on con-G[A7]. Restraining this helix in a linear form (i.e., con-G[A7,E10-K13]) results in a minor reduction in potency. Incorporation of a 7-10 salt-bridge replacement (con-G[K7-E10]) prevents helix formation in aqueous solution and produces a peptide with low potency. Peptides with the Leu5-Tyr5 substitution also have low potencies (con-G[Y5,A7] and con-G[Y5,K7]) indicating that Leu5 in con-G is important for full antagonist behavior. We have also shown that the Gla-Ala7 substitution increases potency, whereas the Gla-Lys7 substitution has no effect. Con-G and con-G[K7] both exhibit selectivity between NMDA subtypes from mid-frontal and superior temporal gyri, but not between sensorimotor and mid-frontal gyri. Asn8 and/or Asn17 appear to be important for the ability of con-G to function as an inhibitor of polyamine-stimulated [3H]MK-801 binding, but not in maintaining secondary structure. The presence of Ca2+ does not increase the potencies of con-G and con-T for NMDA receptors but does stabilize the helical structures of con-G, con-G[D8,D17], and, to a lesser extent, con-G[A7]. The NMR data support the existence of at least two independent Ca2+-chelating sites in con-G, one involving Gla7 and possibly Gla3 and the other likely to involve Gla10 and/or Gla14.

Determination of chemical shielding tensor of an indole carbon and application of tryptophan orientation of a membrane peptide

Using tryptophan C-13-enriched at the C-4 (C epsilon(3)) of the indole, the orientation of the C epsilon(3) chemical shift tensor relative to the C epsilon(3)-H dipolar axis was determined from the C-13 chemical shift/C-13-H-1 dipolar 2D NMR powder pattern. The principal values obtained were 208, 137 and 15 ppm with sigma(33) perpendicular to the indole plane, and sigma(11) (least shielded direction) 5 degrees off the C epsilon(3)-H bond toward C xi(3). The side off the C epsilon(3)-H bond was determined by comparing the reduced chemical shift anisotropies obtained by solid-state NMR and from molecular dynamics calculations of [4-C-13] tryptophans in gramicidin A aligned in phospholipid membranes. (C) 1999 Elsevier Science B.V. All rights reserved.

Effects of beta-escin and saponin on the transverse-tubular system and sarcoplasmic reticulum membranes of rat and toad skeletal muscle

Mechanically skinned skeletal muscle fibres from rat and toad were exposed to the permeabilizing agents beta-escin and saponin. The effects of these agents on the sealed transverse tubular system (t-system) and sarcoplasmic reticulum (SR) were examined by looking at changes in the magnitude of the force responses to t-system depolarization, the time course of the fluorescence of fura-2 trapped in the sealed t-system, and changes in the magnitude of caffeine-induced contractures following SR loading with Ca2+ under defined conditions. In the presence of 2 mu g ml(-1) beta-escin and saponin, the response to t-system depolarization was not completely abolished, decreasing to a plateau, and a large proportion of fura-2 remained in the sealed t-system. At 10 mu g ml(-1), both agents abolished the ability of both rat and toad preparations to respond to t-system depolarization after 3 min of exposure, but a significant amount of fura-2 remained in sealed t-tubules even after exposure to 100 mu g ml(-1) beta-escin and saponin for 10 min. beta-Escin took longer than saponin to reduce the t-system depolarizations and fura-2 content of the sealed t-system to a similar level. The ability of the SR to load Ca2+ was reduced to a lower level after treatment with beta-escin than saponin. This direct effect on the SR occurred at much lower concentrations for rat (2 mu g ml(-1) beta-escin and 10 mu g ml(-1) saponin) than toad (10 mu g ml(-1) beta-escin and 150 mu g ml(-1) saponin). The reverse order in sensitivities to beta-escin and saponin of t-system and SR membranes indicates that the mechanisms of action of beta-escin and saponin are different in the two types of membrane. In conclusion, this study shows that: (1) beta-escin has a milder action on the surface membrane than saponin; (2) beta-escin is a more potent modifier of SR function; (3) simple permeabilization of membranes is not sufficient to explain the effects of beta-escin and saponin on muscle membranes; and (4) the t-system network within muscle fibres is not a homogeneous compartment.