Numerical study of hydrogenic effective mass theory for an impurity P donor in Si in the presence of an electric field and interfaces

In this paper we examine the effects of varying several experimental parameters in the Kane quantum computer architecture: A-gate voltage, the qubit depth below the silicon oxide barrier, and the back gate depth to explore how these variables affect the electron density of the donor electron. In particular, we calculate the resonance frequency of the donor nuclei as a function of these parameters. To do this we calculated the donor electron wave function variationally using an effective-mass Hamiltonian approach, using a basis of deformed hydrogenic orbitals. This approach was then extended to include the electric-field Hamiltonian and the silicon host geometry. We found that the phosphorous donor electron wave function was very sensitive to all the experimental variables studied in our work, and thus to optimize the operation of these devices it is necessary to control all parameters varied in this paper.

4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes from the cane beetle Antitrogus parvulus - Cuticular hydrocarbons with unprecedented structure and stereochemistry

[GRAPHICS] The major cuticular hydrocarbons from the cane beetle species Antitrogus parvulus were deduced to be 4,6,8,10,16,18-hexa- and 4,6,8,10,16-pentamethyldocosanes 2 and 3, respectively. Isomers of 2,4,6,8-tetramethylundecanal 27, 36, and 37, derived from 2,4,6-trimethylphenol, were coupled with the phosphoranes 28 and 29 to furnish alkenes and, by reduction, diastereomers of 2 and 3. Chromatographic and spectroscopic comparisons confirmed 2 as either 6a or 6b and 3 as either 34a or 34b.

Synthesis, stability, antiviral activity, and protease-bound structures of substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease

Three new peptidomimetics (1-3) have been developed with highly stable and conformationally constrained macrocyclic components that replace tripeptide segments of protease substrates. Each compound inhibits both HIV-1 protease and viral replication (HIV-I, HIV-2) at nanomolar concentrations without cytotoxicity to uninfected cells below 10 mu M. Their activities against HIV-1 protease (K-i 1.7 nM (1), 0.6 nM (2), 0.3 nM (3)) are 1-2 orders of magnitude greater than their antiviral potencies against HIV-1-infected primary peripheral blood mononuclear cells (IC50 45 nM (1), 56 nM (2), 95 nM (3)) or HIV-1-infected MT2 cells (IC50 90 nM (1), 60 nM (2)), suggesting suboptimal cellular uptake. However their antiviral potencies are similar to those of indinavir and amprenavir under identical conditions. There were significant differences in their capacities to inhibit the replication of HIV-1 and HIV-2 in infected MT2 cells, 1 being ineffective against HIV-2 while 2 was equally effective against both virus types. Evidence is presented that 1 and 2 inhibit cleavage of the HIV-1 structural protein precursor Pr55(gag) to p24 in virions derived from chronically infected cells, consistent with inhibition of the viral protease in cells. Crystal structures refined to 1.75 Angstrom (1) and 1.85 Angstrom (2) for two of the macrocyclic inhibitors bound to HIV-1 protease establish structural mimicry of the tripeptides that the cycles were designed to imitate. Structural comparisons between protease-bound macrocyclic inhibitors, VX478 (amprenavir), and L-735,524 (indinavir) show that their common acyclic components share the same space in the active site of the enzyme and make identical interactions with enzyme residues. This substrate-mimicking minimalist approach to drug design could have benefits in the context of viral resistance, since mutations which induce inhibitor resistance may also be those which prevent substrate processing.

NMR analysis of covalent intermediates in thiamin diphosphate enzymes

Enzymic catalysis proceeds via intermediates formed in the course of substrate conversion. Here, we directly detect key intermediates in thiamin diphosphate (ThDP)-dependent enzymes during catalysis using H-1 NMR spectroscopy. The quantitative analysis of the relative intermediate concentrations allows the determination of the microscopic rate constants of individual catalytic steps. As demonstrated for pyruvate decarboxylase (PDC), this method, in combination with site-directed mutagenesis, enables the assignment of individual side chains to single steps in catalysis. In PDC, two independent proton relay systems and the stereochemical control of the enzymic environment account for proficient catalysis proceeding via intermediates at carbon 2 of the enzyme-bound cofactor. The application of this method to other ThDP-dependent enzymes provides insight into their specific chemical pathways.

Characterization of the acidic properties of mesoporous aluminosilicates synthesized from leached saponite with additional aluminum incorporation

The acidic properties of hexagonal mesoporous aluminosilicates synthesized via a new successful short time synthesis route using leached saponite and a low concentration of surfactant are thoroughly investigated. The resulting aluminosilicate mesoporous materials with high Si/Al ratios of around 11 have a maximal surface area of 1130 m(2)/g, a pore volume of 0.92 cm(3)/g, and a narrow pore size distribution at around 3 nm. The replacement of the sodium ions, present as counterions in the synthesized aluminosilicates, with protons imparts useful catalytic acidity. This acidity is extensively studied with FTIR spectroscopy after adsorption of ammonia and cyclohexylamine, while deuterated acetonitrile differentiates between Bronsted and Lewis acidity. Al-27 NMR spectroscopy determined the coordination of the aluminum in the FSM materials. Simultaneously the effect of an additional Al incorporation, utilizing sodium aluminate, aluminum nitrate, and aluminum isopropoxide is studied. From an acidic point of view, the incorporation with Al(NO3)(3) appears to be the most optimal, as the sample has a very high amount of acid sites (1.3 mmol/g). Investigating the nature of the acid sites it is found that in all samples except the one incorporated with Al(NO3)(3), more Bronsted than Lewis sites are present, both sites being quite acidic as they resist desorption temperatures up to 300 degreesC. Probing the coordination and location of the Al atoms, all the catalysts appeared to have mostly tetrahedral aluminum, up to 95% of the total Al amount for the proton exchanged AI(NO3)(3) incorporated sample.

Radio frequency plasma-induced hydrogen bonding on kaolinite

The radio frequency (RF) plasma-modified surfaces of kaolinite were investigated by diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) and deuteration techniques to determine the nature of RF plasma-induced surface functional groups, the altered sites in the lattice, and interaction mechanism between RF plasma and the surface of the kaolinite. It has been concluded that the RF plasma-induced infrared (IR) vibration absorption bands at 2805, 3010, and 3100 cm(-1) are attributable to the stretching vibration of hydrogen-bonded hydroxyl groups, and the band at 1407 cm(-1) is attributable to the bending vibration of (HO-)Al-O or (HO-)Si-O groupings with hydrogen-bonded hydroxyl groups. Structural alteration occurred on both the surface and subsurface region of the kaolinite during RF plasma treatment. Further structural alteration or adjustment was also observed on well-modified and well-deuterated kaolinite. There are two types of OD bands visible in the DRIFT spectra of this kaolinite, one type which decreased rapidly as a function of time in moist air, and the other which remained unchanged during the measurement. Furthermore, the appearance of broad IR bands at 3500-3100 cm(-1) as a result of deuteration is evidence of structural disturbance by RF plasma treatment lattice deuteration. An RF plasma-induced hydrogen bonding model on the surface of the kaolinite is proposed.

Spinal stiffness changes throughout the respiratory cycle

Posteroanterior stiffness of the lumbar spine is influenced by factors, including trunk muscle activity and intra-abdominal pressure (IAP). Because these factors vary with breathing, this study investigated whether stiffness is modulated in a cyclical manner with respiration. A further aim was to investigate the relationship between stiffness and IAP or abdominal and paraspinal muscle activity. Stiffness was measured from force-displacement responses of a posteroanterior force applied over the spinous process of L-2 and L-4. Recordings were made of IAP and electromyographic activity from L-4/L-2 erector spinae, abdominal muscles, and chest wall. Stiffness was measured with the lung volume held at the extremes of tidal volume and at greater and lesser volumes. Stiffness at L-4 and L-2 increased above base-level values at functional residual capacity (L-2 14.9 N/mm and L-4 15.3 N/mm) with both inspiratory and expiratory efforts. The increase was related to the respiratory effort and was greatest during maximum expiration (L-2 24.9 N/mm and L-4 23.9 N/mm). The results indicate that changes in trunk muscle activity and IAP with respiratory efforts modulate spinal stiffness. In addition, the diaphragm may augment spinal stiffness via attachment of its crural fibers to the lumbar vertebrae.

Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites

Disposition kinetics of [H-3] palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [H-3] palmitate and its low-molecular-weight metabolites, and several physiologically based pharmacokinetic models. The level of liver fatty acid binding protein (L-FABP), other intrahepatic binding proteins (microsomal protein, albumin, and glutathione S-transferase) and the outflow profiles of [H-3] palmitate and metabolites were measured in four experimentalgroups of rats: 1) males; 2) clofibrate-treated males; 3) females; and 4) pregnant females. A slow-diffusion/bound model was found to better describe the hepatic disposition of unchanged [H-3] palmitate than other pharmacokinetic models. The L-FABP levels followed the order: pregnant female > clofibrate-treated male > female > male. Levels of other intrahepatic proteins did not differ significantly. The hepatic extraction ratio and mean transit time for unchanged palmitate, as well as the production of low-molecular-weight metabolites of palmitate and their retention in the liver, increased with increasing L-FABP levels. Palmitate metabolic clearance, permeability-surface area product, retention of palmitate by the liver, and cytoplasmic diffusion constant for unchanged [H-3] palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [H-3] palmitate and its low-molecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins.

Physical Activity and Bone Mineral Accrual During Childhood and Adolescence

The epidemic that is osteoporosis has led to an increasing interest in bone mineral, and the factors that influence the levels of bone mineral, in recent years. While it is unrealistic to try and turn back the clock, a return to an increased level of physical activity may be an important consideration in terms of skeletal health. Peak bone mass is largely determined by heredity, but lifestyle and dietary patterns also influence the level of bone mineral accrued during the growing years. In this review, we summarize the evidence that vigorous weight-bearing physical activity and adequate calcium intake represent the best possibility for enhancing the attainment of an optimal level of bone mineral, within genetic limits.

The Lake Tekapo experiment (LTEX): An investigation of atmospheric boundary layer processes in complex terrain

A research program on atmospheric boundary layer processes and local wind regimes in complex terrain was conducted in the vicinity of Lake Tekapo in the southern Alps of New Zealand, during two 1-month field campaigns in 1997 and 1999. The effects of the interaction of thermal and dynamic forcing were of specific interest, with a particular focus on the interaction of thermal forcing of differing scales. The rationale and objectives of the field and modeling program are described, along with the methodology used to achieve them. Specific research aims include improved knowledge of the role of surface forcing associated with varying energy balances across heterogeneous terrain, thermal influences on boundary layer and local wind development, and dynamic influences of the terrain through channeling effects. Data were collected using a network of surface meteorological and energy balance stations, radiosonde and pilot balloon soundings, tethered balloon and kite-based systems, sodar, and an instrumented light aircraft. These data are being used to investigate the energetics of surface heat fluxes, the effects of localized heating/cooling and advective processes on atmospheric boundary layer development, and dynamic channeling. A complementary program of numerical modeling includes application of the Regional Atmospheric Modeling System (RAMS) to case studies characterizing typical boundary layer structures and airflow patterns observed around Lake Tekapo. Some initial results derived from the special observation periods are used to illustrate progress made to date. In spite of the difficulties involved in obtaining good data and undertaking modeling experiments in such complex terrain, initial results show that surface thermal heterogeneity has a significant influence on local atmospheric structure and wind fields in the vicinity of the lake. This influence occurs particularly in the morning. However, dynamic channeling effects and the larger-scale thermal effect of the mountain region frequently override these more local features later in the day.

Intramolecular electron transfer in a bacterial sulfite dehydrogenase

Sulfite dehydrogenase (SDH) from Starkeya novella, a sulfite-oxidizing molybdenum-containing enzyme, has a novel tightly bound αβ-heterodimeric structure in which the Mo cofactor and the c-type heme are located on different subunits. Flash photolysis studies of intramolecular electron transfer (IET) in SDH show that the process is first-order, independent of solution viscosity, and not inhibited by sulfate, which strongly indicates that IET in SDH proceeds directly through the protein medium and does not involve substantial movement of the two subunits relative to each other. The IET results for SDH contrast with those for chicken and human sulfite oxidase (SO) in which the molybdenum domain is linked to a b-type heme domain through a flexible loop, and IET shows a remarkable dependence on sulfate concentration and viscosity that has been ascribed to interdomain docking. The results for SDH provide additional support for the interdomain docking hypothesis in animal SO and clearly demonstrate that dependence of IET on viscosity and sulfate is not an inherent property of all sulfite-oxidizing molybdenum enzymes.

3-pyridylcarbene and 3-pyridylnitrene: Ring opening to nitrile ylides

Photolysis of 3-pyridyldiazomethane in an Ar matrix at 7-10 K gives 3-pyridylcarbene. Further photolysis causes ring opening to nitrile ylide 26 (formonitrile pent-2-en-4-ynylide) as the major reaction together with a minor amount of ring expansion to 1-azacyclohepta-1,3,4,6-tetraene, 27. Matrix photolysis of 3-azidopyridine leads to ring opening to formonitrile N-cyanovinylmethylide, 33.

2-quinolyl- and 1-isoquinolylnitrenes: Ring expansion and ring opening in heteroarylnitrenes

Argon matrix photolysis of tetrazolo[1,5-a]quinoline 8 and tetrazolo[5,1-a]isoquinoline 7 causes nitrogen elimination and ring expansion to 1,3-diazabenzo[d]cyclohepta-1,2,4,6-tetraene 13. The photolysis of tetrazolo[5,1-a]isoquinoline 7 also causes ring opening to o-cyanophenylketenimine 22. Mechanisms of ring opening of heteroarylnitrenes are discussed.

Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency

Glucocorticoids are pivotal for adipose tissue development. Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue. In humans, both genetic CBG deficiency and suppressed CBG concentrations in hyperinsulinemic states are associated with obesity. We hypothesized that CBG deficiency in humans modulates the response of human preadipocytes to glucocorticoids, predisposing them to obesity. We compared normal preadipocytes with subcultured preadipocytes from an individual with the first ever described complete deficiency of CBG due to a homozygous null mutation. CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor-gamma-mediated differentiation than normal preadipocytes. CBG was not expressed in normal human preadipocytes. Glucocorticoid receptor number and binding characteristics and 11beta-hydroxysteroid dehydrogenase activity were similar for CBG-negative and normal preadipocytes. We propose that the increased proliferation and enhanced differentiation of CBG-negative preadipocytes may promote adipose tissue deposition and explain the obesity seen in individuals with genetic CBG deficiency. Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia.

Synthesis and characterization of delta-atracotoxin-ar1a, the lethal neurotoxin from venom of the Sydney funnel-web spider (Atrax robustus)

delta-Atracotoxin-Ar1a (delta-ACTX-Ar1a) is the major polypeptide neurotoxin isolated from the venom of the male Sydney funnel-web spider, Atrax robustus. This neurotoxin targets both insect and mammalian voltage-gated sodium channels, where it competes with scorpion alpha-toxins for neurotoxin receptor site-3 to slow sodium-channel inactivation. Progress in characterizing the structure and mechanism of action of this toxin has been hampered by the limited supply of pure toxin from natural sources. In this paper, we describe the first successful chemical synthesis and oxidative refolding of the four-disulfide bond containing delta-ACTX-Ar1a. This synthesis involved solid-phase Boc chemistry using double coupling, followed by oxidative folding of purified peptide using a buffer of 2 M GdnHCl and glutathione/glutathiol in a 1:1 mixture of 2-propanol (pH 8.5). Successful oxidation and refolding was confirmed using both chemical and pharmacological characterization. Ion spray mass spectrometry was employed to confirm the molecular weight. H-1 NMR analysis showed identical chemical shifts for native and synthetic toxins, indicating that the synthetic toxin adopts the native fold. Pharmacological studies employing whole-cell patch clamp recordings from rat dorsal root ganglion neurons confirmed that synthetic delta-ACTX-Ar1a produced a slowing of the sodium current inactivation and hyperpolarizing shifts in the voltage-dependence of activation and inactivation similar to native toxin. Under current clamp conditions, we show for the first time that delta-ACTX-Ar1a produces spontaneous repetitive plateau potentials underlying the clinical symptoms seen during envenomation. This successful oxidative refolding of synthetic delta-ACTX-Ar1a paves the way for future structure-activity studies to determine the toxin pharmacophore.