bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of non-equilibrium transient effects on measurements of vibrational relaxation times and of dissociation rate constants
Authors: Teitelbaum Heshel
Published: May 2006

A semi-empirical analysis based on a rate law for vibrational relaxation of dissociating simple harmonic oscillators allows for a detailed study of measurements of vibrational relaxation times τ and of steady dissociation rate coefficients k0. It is shown that non-equilibrium populations of vibrational energy levels prevent attainment of the thermodynamically expected equilibrium energy. Even under near-isothermal and mild conditions, [Formula: see text], serious experimental errors result when the Bethe–Teller relaxation rate law is used. Closed form expressions are given which permit evaluation of these errors. Measurements should be analyzed using the rate law[Formula: see text]where ε is the vibrational energy per molecule, τ the relaxation time, kd the non-equilibrium rate coefficient, ετ the thermodynamically expected vibrational energy at temperature T, and (ε* + hv) the energy just above the dissociation limit. It is also shown that if[Formula: see text]a local minimum and maximum are predicted for measured density gradients in shock tube dissociations of diatomic molecules, where tine is the incubation time, D′ the effective dissociation energy, and x0 the mole fraction of dissociating molecules in an inert diluent. Expressions are given for extracting incubation times and rate constants from such studies when [Formula: see text]. Analysis of experimental data actually showing such phenomena (J. Chem Phys. 55, 4017 (1971)) is carried out. There are indications that any analysis which does not explicitly account for transient effects could result in errors in measured k0's of factors of 2 or more.
Alkaline oxidation of diastereoisomeric 4a,10a-dihydrofusarubins to norjavanicin, fusarubin, and a new antibiotic isofusarubin: nonenzymic formation of products in Fusariumsolani cultures
Authors: McCulloch Archibald W. , McInnes A. Gavin , Smith Donald G. , Kurobane Itsuo , Vining Leo C.
Published: May 2006

Conversion of two diastereoisomeric 4a,10a-dihydrofusarubins, produced by Fusariumsolani, to fusarubin, norjavanicin, and a new compound, isofusarubin ((E)-6,7-dihydro-5,8-dihydroxy-2-methoxy-6-methylene-7-(2-oxopropylidene)-1,4-naphthalenedione), has been studied under a variety of culture conditions and in alkaline solution. Antibiotic and phototoxic activities of these compounds were determined and the structures of isofusarubin and of anhydroisofusarubin mono- and diacetates were elucidated by 1H and 13C nmr.
Enzymes in organic synthesis. 28. Reinvestigation of the horse liver alcohol dehydrogenase-catalyzed reductions of 2-alkylcyclohexanones.Identification of cis-alkylcyclohexanols as minor products
Authors: Jones J. Bryan , Takemura Tetsuo
Published: May 2006

The formation of cis-2-alkylcyclohexanol products from horse liver alcohol dehydrogenase-catalyzed reductions of 2-alkylcyclohexanones has been detected for the first time. The cis-alcohols are minor (<4%) products, with the isomeric trans-products being heavily predominant under all conditions. cis-Alcohol production can be suppressed by suitable manipulation of the reaction conditions. Exclusive formation of the trans-alcohols is favoured by operating in an appropriate buffer such as Tris-HCl at the lowest [E]/[S] and pH conditions possible, and by minimizing the reaction time. The results parallel the cis-alcohol formation observed previously with the analogous 3-alkyltetrahydrothiopyran-4-one substrates.
Structural studies of organoboron compounds. XII. Crystal and molecular structures of (acetylacetonato)diphenylboron and (tropolonato)diphenylboron
Authors: Rettig Steven J. , Trotter James
Published: May 2006

There are two crystalline modifications of (acetylacetonato)diphenylboron: triclinic, a = 8.3557(8), b = 9.3519(8), c = 9.6103(9) Å, α = 96.094(5), β = 94.904(6), γ = 93.489(6)°, Z = 2, space group [Formula: see text], and monoclinic, a = 11.6329(11), b = 17.1628, c = 7.6542(6) Å, β = 97.669(4)°, Z = 4, space group P21/c. Crystals of (tropolonato)diphenylboron are monoclinic, a = 12.1596(5), b = 10.2614(4), c = 12.4883(6) Å, β = 100.965(2)°, Z = 4, space group P21/c. All three structures were solved by direct methods and were refined by full-matrix least-squares procedures to R values of 0.046, 0.041, and 0.035 for 2465, 2124, and 1722 reflections with I ≥ 3σ(I) respectively. Each structure consists of discrete molecules containing tetrahedrally coordinated boron atoms, both the acetylacetonato and tropolonato moieties being delocalized and symmetric. The chelate rings in both forms of (acetylacetonato)-diphenylboron have distorted B-envelope conformations while the chelate ring in (tropolonato)diphenylboron is essentially planar. The mean B—O and B—C distances (corrected for libration) are: 1.543(4) and 1.605(4) Å in triclinic, 1.533(3) and 1.607(4) Å in monoclinic (acetylacetonato)diphenylboron, and 1.555(11) and 1.605(6) Å in (tropolonato)diphenylboron.
Five-membered ring annulation via thermal rearrangement of β-cyclopropyl α,β-unsaturated ketones. A formal total synthesis of the sesquiterpenoid (±)-zizaene
Authors: Piers Edward , Banville Jacques , Lau Cheuk Kun , Nagakura Isao
Published: May 2006

Treatment of the β-iodo enones 7–10 with lithium (phenylthio)(cyclopropyl)cuprate provided excellent yields of the corresponding β-cyclopropyl α,β-unsaturated ketones 11–14, respectively. When 3-isopropenyl-2-cyclohexen-1-one (16) was allowed to react with dimethyloxosulfonium methylide in dimethyl sulfoxide – tetrahydrofuran, 3-(1-methylcyclopropyl)-2-cyclohexen-1-one (17) was produced in 59% yield. Although thermal rearrangement (~425–450 °C) of compounds 11 and 17 produced high yields of the annulation products 19 and 22, respectively, similar reactions involving the β-cyclopropyl enones 12 and 13 were not efficient in terms of production of the corresponding bicyclic systems (23, 26, and/or 27, respectively). In these cases, predominant (24 + 25 from 12) or significant (28 + 29 from 13) amounts of monocyclic dienones were formed. The annulation product 22 served as a convenient starting material for a new formal total synthesis of the sesquiterpenoid (±)-zizaene (30). Conjugate addition of lithium divinylcuprate to 22 afforded the ketone 36 which was converted by standard methods (via 38 and 39) into the enone 40. Treatment of the latter substance with thiophenol in the presence of tetra-n-butylammonium fluoride gave 41, which was transformed via ketalization (41 → 42), hydroboration(42 → 43), tosylation (43 → 44), and oxidation (44 → 45) into the sulfone 45. When the latter compound was treated with potassium tert-butoxide in hexamethylphosphoramide, the tricyclic ketal sulfone 46 was produced in 85% yield. Reduction of 46 with sodium amalgam afforded the ketal 47, which upon hydrolysis under mild conditions gave the ketone 32. Treatment of the latter substance with sodium methoxide in methanol provided a 1:2 mixture of the epimeric ketones 31 and 32, which had been converted previously by Coates and Sowerby into (±)-zizaene (30).
A proton relaxation study of the conformations of some purine mononucleotides in aqueous solution
Authors: Geraldes C. F. G. C. , Santos H. , Xavier A. V.
Published: May 2006

A method is described by which conformationally averaged interproton distances in mononucleotides are obtained from measured proton spin-lattice relaxation times and published crystal coordinates of selected mononucleotides. The glycosil conformations of adenosine in D2O and DMSO-d6 and of 5′-AMP, 5′-GMP, 3′-AMP, and 2′-AMP in D2O are examined by quantitative analysis of the conformationally averaged interproton distances in terms of population distributions obtained from potential energy calculations. 5′-AMP strongly prefers a single glycosyl conformation in the anti range. Besides the anti conformation, 5′-GMP has a secondary minimum in the syn region. 3′-AMP, 2′-AMP, and adenosine have more latitude in their glycosyl torsion angle values, with both the syn and anti regions highly populated.
Polymer supported enantioselective reactions. III. Protonation of lithioenamine derivatives of racemic 2-methylcyclohexanone
Authors: McArthur Colin R. , Jiang Ji-Long , Leznoff Clifford C.
Published: May 2006

Asymmetric protonations, with enantioselectivities ranging to 90%, were observed in reactions of lithioenamines derived from imines of racemic 2-methylcyclohexanone and insoluble cross-linked copolymers of polystyrene and divinylbenzene substituted with (S)-2-aminoalkoxymethyl groups.
A carbon-13 nuclear magnetic resonance study of a series of 5-substituted benzimidazoles
Authors: Blackburn Barry J. , Ankrom Douglas W. , Hutton Harold M.
Published: May 2006

Carbon-13 nmr chemical shift assignments are reported for a series of 5-substituted benzimidazoles, 2-methylbenzimidazole, and 5,6-dimethylbenzimidazole. By employing the three-parameter equation of Smith and Proulx, the chemical shifts of all the ring carbons of the 5-substituted compounds are correlated with F and R of Swain and Lupton and Q of Schaefer; only the ipso carbon, C-5, has chemical shifts with a correlation coefficient less than 0.953. These correlations are compared with those obtained from the Swain–Lupton and Taft relationships; in general those from the latter two approaches are found to be less satisfactory. Correlations of the same chemical shifts with excess charge density values, calculated at the INDO level of approximation, are also presented.
A 1H and 13C nuclear magnetic resonance study of nucleosides with methylated pyrimidine bases
Authors: Hruska Frank E. , Blonski Wayne J. P.
Published: May 2006

Alkylated pyrimidine bases are of interest from the viewpoint of mutagenesis and carcinogenesis. 1H nuclear magnetic resonance data are presented for a series of ribosides and arabinosides alkylated at the O2,O4, N3, and C5 positions of the pyrimidine base. The data provide information about the stereochemical effects of base methylation. The J(5—6) proton coupling constants show that O-alkylation leads to a decrease in the π-bond order of the C5—C6 bond. The 13C chemical shifts are related to the tautomeric changes effected by O-alkylation.
Mechanistic studies in strong acids. VIII. Hydrolysis mechanisms for some thiobenzoic acids and esters in aqueous sulfuric acid, determined using the excess acidity method
Authors: Cox Robin A. , Yates Keith
Published: May 2006

The excess acidity method has been applied to hydrolysis rate data, obtained as a function of medium composition, for four thiobenzoic acids, thioacetic acid, eight ethyl thiolbenzoates, and eight ethyl thionbenzoates in aqueous sulfuric acid. The mechanistic behaviour thus revealed has both similarities to and differences from that of a typical ester like ethyl benzoate, which gives benzoic acid by an A-2 reaction involving two water molecules in weak acid, and by A-1 acylium ion formation in strong acid. The thioacids follow this behaviour, except that the A-2 process involves three water molecules, and that the mechanistic changeover occurs in 60% rather than 80% acid. The A-2 process for the ethyl thiolbenzoates is slow; the major hydrolysis mechanism is acylium ion formation, not in an A-1 reaction but by a concerted A-SE2 process involving both proton transfer to sulfur and carbon–sulfur bond breaking. The major proton transfer agent is the undissociated sulfuric acid molecule. The thionbenzoate esters, in contrast, undergo very fast A-2 hydrolysis; so fast, in fact, that the initial protonation of sulfur is the rate-determining step in acids more dilute than about 62% w/w. It appears that proton transfer to sulfur is a comparatively slow process.
L'enrobage moléculaire: complexation du cation sodium par le dibenzo-24-couronne-8
Authors: Bisnaire Michel , Detellier Christian , Nadon Dominique
Published: May 2006

Structure and microdynamics in solution of the dibenzo-24-crown-8 – sodium perchlorate complex have been studied by Na-23 and C-13 nmr. In all solvents (acetone, acetonitrile, pyridine, nitromethane, propylene carbonate, and chloroform-d) and in the binary mixtures acetone/pyridine, acetonitrile/nitromethane, propylene carbonate/methanol, the crown wraps around the sodium cation and expels the conjugate anion and the solvent molecules from the cation coordination sphere. Measurements of Na-23 quadrupolar and C-13 dipole–dipole relaxation times give the effective correlation time of the complex in CDCl3 solution (65 ± 11 ps) and the Na-23 quadrupolar coupling constant in all those solvents and binary mixtures (0.8–1.2 MHz). The sodium coordination shell is completely frozen during a time superior to the reorientational correlation time.
The influence of crown ethers on the kinetics of E1cB and E2 β-elimination reactions of di(4-nitrophenyl)fluoroethanes with sodium methoxide in methanol
Authors: Leffek Kenneth T. , Schroeder Grzegorz
Published: May 2006

The addition of crown ethers 1,4,7,10,13-pentaoxacyclopentadecane (15C5) and 1,4,7,10,13,16-hexaoxacyclooctadecane (18C6) in quantities equimolar to the base, to β-elimination reactions of 1,1,1-trifluoro-2,2-di(4-nitrophenyl)ethane and 1-fluoro-2,2-di(4-nitrophenyl)ethane promoted by sodium methoxide in methanol, has been investigated. In the E2 reaction of the monofluoro compound, the crown ethers caused no change in the kinetic order and only small changes in the second-order rate constants and activation parameters. The primary deuterium isotope effect was also unaltered by the presence of crown ethers.For the (E1cB)R reaction of the trifluoro compound, no change in kinetic order was found, but slightly larger rate constant changes and an increase in the isotope effect from kH/kD = 1.0 to 1.25 at 25 °C was observed. This is interpreted as an alteration in mechanism from (E1cB)R towards (E1cB)I.
Phosphonodipeptides: synthesis and separation of diastereoisomers
Authors: Kafarski Paweł , Lejczak Barbara , Mastalerz Przemsław , Szewczyk Jerzy , Wasielewski Czesław
Published: May 2006

Diastereoisomeric mixtures of phosphonodipeptides, prepared from racemic dialkyl 1-aminoalkanephosphonates, were separated by ion-exchange column chromatography. Phosphonodipeptides were found to be much more readily available from dialkyl 1-aminoalkanephosphonates than from the corresponding free acids and the mixed carboxylic – carbonic anhydride method was found to be the most effective one.
The reaction of heptachlor on alumina impregnated with sulphuric acid in the presence of various aromatic compounds
Authors: ApSimon John W. , Chau Alfred S. , Sampson Robin , Tze Hung , Fruchier Alain
Published: May 2006

not available
NON-PERTURBATIVE QCD CHARGE ASYMMETRIC CORRECTIONS TO THE NN SCATTERING LENGTHS
Authors: RIAZUDDIN  , FAYYAZUDDIN
Published: May 2006

The effect of the vacuum asymmetry [Formula: see text] on π0pp and π0nn coupling constants has been estimated in the QCD sum rules approach. This effect can contribute to charge symmetry breaking in nuclear forces (CSB). The experimental information on CSB is used to estimate εd and the other vacuum asymmetry. [Formula: see text]. It is shown that the values of εs larger than 0.3 still allowed by QCD sum rules in light baryon and meson sectors are not possible.
ELECTROSPRAYING A NANOPARTICULATE SUSPENSION
Authors: JAYASINGHE S. N.
Published: May 2006

This paper reports an investigation into electrospraying a nanosuspension containing nanoparticles sized at 5 nm and suspended in a polymer grade ethylene glycol. Hence, the processing of this nanosuspension in the stable cone-jet mode having an amorphous silica powder loading of 30 wt.% is elucidated. A comparison is made with established literature on jet break-up to identify the break-up mechanism in this investigation. The ensuing electrospray characteristics for both the polymer grade ethylene glycol and the nanosuspension are also presented. Using the data of collected droplet relics together with a volume equivalence method, the generated droplet sizes are estimated for both media and are compared with the well-known theoretical expression for calculating the droplet sizes generated for that respective jet break-up regime and medium. Finally, transmission electron microscopy of the collected deposits concludes the discussion presented in this investigation.
TENSILE PROPERTIES AND ELECTRONIC STRUCTURES OF C240 NANOTUBE AND 4C60 FULLERENE POLYMERS
Authors: SHEN HAIJUN
Published: May 2006

The classical MD (Molecular Dynamics) method was used to simulate the tension of three kinds of C 240 isomers, i.e., C 240 nanotube, chain-like 4C 60 fullerene polymer and peanut-like 4C 60 fullerene polymer. Then, the semi-empirical PM3 method was used to calculate their electronic structures under tension. Lastly, according to the calculated results, their differences in tensile mechanical properties, as well as the change of their FMO (Frontier Molecular Orbital) energy during tension, were discussed. It is shown that: (1) the load-support capability of the C 240 molecules has the order of C 240 nanotube > peanut-like 4C 60 polymer > linear 4C 60 polymer, but their deformation-support capability has the contrary order, (2) of the C 240 isomers, the C 240 nanotube has the best chemical stability, and the chain-like 4C 240 molecule has the worst one, and (3) the deformed C 240 isomers have narrower energy-gap between their LUMO and HOMO, and higher chemical activity.
EFFECTS OF SURFACE OXYGEN ON THE ELECTRONIC PROPERTIES OF SILICON NANOCLUSTERS
Authors: DAI YING , HUANG BAIBIAO , YU LIN , HAN SHENGHAO , DAI DADI
Published: May 2006

We have studied the effects of surface oxygen and its bond structure on the electronic properties of silicon nanoclusters by means of density functional theory calculations. The results of the energy gap as a function of the nanocluster size in hydrogen-terminated and oxygen-adsorbed silicon clusters provide a well interpretation of several experiments. The nature of electronic and optical properties of silicon nanoclusters has been discussed and attributed to the oxygen in both the Si=O double bond structure and Si–O–Si bridge structure.
SPIN IN CARBON NANOTUBE-BASED OSCILLATORS
Authors: XIAO SHAOPING , HAN RAY , HOU WENYI
Published: May 2006

In this paper, molecular dynamics simulations are performed on a [10, 10]/[5, 5] carbon nanotube-based oscillator. In our work, we observed a spin phenomenon of the inner tube when it oscillated in an isolated oscillator system. If there exist a rocking motion when the inner tube started to oscillate, an axial torque would be observed, and it would drive the inner tube to spin. When the oscillation became stable, the torque almost vanished, and the spin was stabilized with a constant frequency of 21.78 GHz. Such a spin phenomenon was also observed when the oscillator system was at a room temperature of 300 K. However, both magnitude and direction of the spin angular velocity varied from time to time, even after the oscillation of the inner tube stopped due to the energy dissipation.
SIMULATED LITHOGRAPHIC PATTERNS FOR PERIODIC ARRAYS OF ATOMIC BEAMS FOCUSED WITH SINGLE ATOMIC LENS
Authors: ALTI KAMLESH , KHARE ALIKA
Published: May 2006

A new configuration of microscopic square arrays of atomic beams in the presence of TEM 00 mode laser, acting as atomic lens, is proposed for atom lithography via dipole force. Simulated patterns using such configuration for rubidium atoms show the formation of nanostructures with periodicity less than λ/2.
EFFECT OF REMOTE BAND COUPLING ON NET RECOMBINATION CURRENT IN TYPE-II HETEROSTRUCTURES
Authors: BOTHA A. E.
Published: May 2006

Exact analytical expressions for the eigenvalues and eigenvectors of the six-band k · p matrix Hamiltonian for narrow-gap III–V semiconductors are used to derive an analytical expression for the transmission coefficient T in type-II heterojunctions. The remote band coupling is included via the two Luttinger-type parameters, γ1 and [Formula: see text]. The expression for T contains two separate contributions: one from electron to light-hole tunneling and the other from electron to heavy-hole tunneling. Using the expression for T, the net recombination current density J is defined and evaluated for the specific case of an InAs/GaSb heterojunction. Ohmic behavior is observed in J for small applied voltages V approximately in the range -0.15 to 0.075 eV. Outside of this range, J changes nonlinearly with respect to changes in V. Comparison of the heavy-hole and light-hole contributions to J shows that the heavy-hole contribution increases J by approximately 10% at room temperature. The results for the InAs/GaSb heterojunction are in qualitative agreement with recent experimental observations.
BINDING ENERGY OF ACCEPTORS IN SEMIMAGNETIC QUANTUM DOTS
Authors: PETER A. JOHN
Published: May 2006

The binding energies of shallow acceptors in Cd 1-x in Mn x in Te/ Cd 1-x out Mn x out Te quantum dots are calculated in the presence of external magnetic fields. Variational calculations are performed within effective mass approximation. The results show that the impurity binding energy (i) increases with the reduction in dot sizes, (ii) decreases with the magnetic field is increased for a given dot, and (iii) reaches a peak value as the dot radius decreases and then diminishes to a limiting value corresponding to the radius for which there are no bound states in the quantum dot. Spin polaronic shifts are estimated with the acceptor envelope function using a mean field theory. These results are compared with the existing literatures.
STUDY OF AFFINITIES BETWEEN SINGLE-WALLED NANOTUBE AND EPOXY RESIN USING MOLECULAR DYNAMICS SIMULATION
Authors: GOU JIHUA , FAN BIN , SONG GANGBING , KHAN AURANGZEB
Published: May 2006

In the processing of carbon nanotube/polymer composites, the interactions between the nanotube and polymer matrix will occur at the molecular level. Understanding their interactions before curing is crucial for nanocomposites processing. In this study, molecular dynamics (MD) simulations were employed to reveal molecular interactions between (10, 10) single-walled nanotube and two kinds of epoxy resin systems. The two kinds of resin systems were EPON 862/EPI-CURE W curing agent (DETDA) and DGEBA (diglycidylether of bisphenol A)diethylenetriamine (DETA) curing agent. The MD simulation results show that the EPON 862, DETDA and DGEBA molecules had strong attractive interactions with single-walled nanotubes and their molecules changed their conformation to align their aromatic rings parallel to the nanotube surface due to π-stacking effect, whereas the DETA molecule had a repulsive interaction with the single-walled nanotubes. The interaction energies of the molecular systems were also calculated. Furthermore, an affinity index (AI) of the average distance between the atoms of the resin molecule and nanotube surface was defined to quantify the affinities between the nanotubes and resin molecules. The MD simulation results show that the EPON 862/EPI-CURE W curing agent system has good affinities with single-walled nanotubes.
CHALCOGENIDE INVERTED OPAL PHOTONIC CRYSTAL AS INFRARED PIGMENTS
Authors: ALIEV A. E. , ZAKHIDOV A. A. , BAUGHMAN R. H. , YABLONOVITCH E.
Published: May 2006

Large surface infrared photonic crystals with reflectance higher than 90% have successfully been synthesized by self-assembling large size SiO 2 spheres, of 0.8-4.5 μm diameters, followed by melt infiltration with the chalcogenide glass Ge 33 As 12 Se 55 and the removal of the SiO 2 spheres by chemical etching. The sphere size and the periodicity of the templates were chosen to guarantee the formation of photonic band gaps of the inverted opals in the targeted IR regions of 3-5 μm and 8-12 μm. Fabrication, structural features and spectral behavior of the reflectance peaks of these chalcogenide glass inverse opals are presented.
MECHANISM AND SIMULATION OF UNIFORM NANOWIRES OF POROUS SILICON GROWTH ON p-Si SUBSTRATE
Authors: HOSSAIN S. M. , DAS J. , DUTTA S. K. , SAHA H.
Published: May 2006

An extension of Beale's and Lehman's model for the formation of porous silicon (PS) layer on p-type substrate is proposed with a view to explain the experimental conditions necessary for obtaining either uniform vertical pores or nonuniform pore branching. A uniformity parameter is defined and correlated with the measured porosity. On the basis of this model, a Monte Carlo simulation algorithm for PS growth has been proposed. The dependence of the porosity, uniformity factor and layer thickness with various formation parameters of PS layer has been studied experimentally. Good agreement between the experimental results and simulation has been found and reported in this paper. Conditions leading to uniform vertical PS growth are predicted from this simple model.
Insulin sensitivity is preserved despite disrupted endothelial function
Authors: Shankar Sudha S. , Considine Robert V. , Gorski J. Christopher , Steinberg Helmut O.
Published: May 2006

It is well established that endothelial dysfunction and insulin resistance go hand in hand. However, it is unclear whether endothelial dysfunction per se is sufficient to impair insulin-mediated glucose uptake. We have previously reported that 4 wk of administration of the human immunodeficiency virus (HIV)-1 protease inhibitor indinavir to HIV-negative subjects induces endothelial dysfunction. Hence, we hypothesized that indinavir-induced endothelial dysfunction was associated with impaired insulin-mediated glucose disposal. We measured insulin-mediated glucose disposal at the level of the whole body, skeletal muscle, and vasculature by performing hyperinsulinemic euglycemic clamp, and vascular function studies, in a separate group of HIV-negative healthy nonobese subjects ( n = 13) before and after 4 wk of daily oral indinavir. Four weeks of indinavir resulted in a 113 ± 29% ( P < 0.01) reduction of endothelium-dependent vasodilation, consistent with our earlier findings. In addition, there was a significant impairment of insulin-mediated vasodilation (101 ± 14% before indinavir vs. 35 ± 15% after indinavir; P < 0.05). However, there was no significant change in insulin-mediated glucose disposal at the level of the whole body (8.9 ± 0.5 before indinavir vs. 8.5 ± 0.6 mg·kg−1·min−1after indinavir; P = 0.4), or skeletal muscle. Furthermore, in a separate group of four HIV-negative healthy nonobese subjects, we found that 4 wk of indinavir has no sustained effect on insulin-stimulated glucose uptake in adipose tissue. Thus our findings indicate that 1) endothelial dysfunction alone is insufficient to impair insulin-mediated glucose disposal, and 2) indinavir-induced endothelial dysfunction is likely due to a direct effect of the drug on the endothelium and is not coupled to the induction of insulin resistance.
Differential coupling of β3A- and β3B-adrenergic receptors to endogenous and chimeric Gαs and Gαi
Authors: Lenard Natalie R. , Prpic Veronica , Adamson Aaron W. , Rogers Richard C. , Gettys Thomas W.
Published: May 2006

Chimeric G proteins made by replacing the COOH-terminal heptapeptide of Gαq with the COOH-terminal heptapeptide of Gαs or Gαi were used to assess the relative coupling of β3-adrenergic receptor (β3-AR) splice variants (β3Aand β3B) to Gαs and Gαi. The Gαq/s and Gαq/i chimeras transformed the response to receptor activation from regulation of adenylyl cyclase to mobilization of intracellular calcium (Ca2+i). Complementary high-throughput and single-cell approaches were used to evaluate agonist-induced coupling of the receptor to the G protein chimeras. In cells stably transformed with rat β3-AR, transfected with the G protein chimeras, and evaluated using a scanning fluorometer, β3-AR-induced coupling to Gαq/s produced a rapid eightfold increase in Ca2+ifollowed by a slow decay to levels 25% above baseline. Gαq/i also linked rat β3-AR to mobilization of Ca2+iin a similar time- and agonist-dependent manner, but the net 2.5-fold increase in Ca2+iwas only 30% of the response obtained with Gαq/s. Activation of the rat β3-AR also increased GTP binding to endogenous Gαi threefold in membranes from CHO cells stably transformed with the receptor. A complementary single-cell imaging approach was used to assess the relative coupling of mouse β3A- and β3B-AR to Gαi under conditions established to produce equivalent agonist-dependent coupling of the receptor splice variants to Gαq/s and to increases in intracellular cAMP through endogenous Gαs. The β3A- and β3B-AR coupled equivalently to Gαq/i, but the temporal patterns of Ca2+imobilization indicated that coupling was significantly less efficient than coupling to Gαq/s. Collectively, these findings indicate less efficient but equivalent coupling of β3A- and β3B-AR to Gαi vs. Gαs and suggest that differential expression of the splice variants would not produce local differences in signaling networks linked to β3-AR activation.
Overexpression of acyl-CoA synthetase-1 increases lipid deposition in hepatic (HepG2) cells and rodent liver in vivo
Authors: Parkes Heidi A. , Preston Elaine , Wilks Donna , Ballesteros Mercedes , Carpenter Lee , Wood Leonie , Kraegen Edward W. , Furler Stuart M. , Cooney Gregory J.
Published: May 2006

Accumulation of intracellular lipid in obesity is associated with metabolic disease in many tissues including liver. Storage of fatty acid as triglyceride (TG) requires the activation of fatty acids to long-chain acyl-CoAs (LC-CoA) by the enzyme acyl-CoA synthetase (ACSL). There are five known isoforms of ACSL (ACSL1, -3, -4, -5, -6), which vary in their tissue specificity and affinity for fatty acid substrates. To investigate the role of ACSL1 in the regulation of lipid metabolism, we used adenoviral-mediated gene transfer to overexpress ACSL1 in the human hepatoma cell-line HepG2 and in liver of rodents. Infection of HepG2 cells with the adenoviral construct AdACSL1 increased ACSL activity >10-fold compared with controls after 24 h. HepG2 cells overexpressing ACSL1 had a 40% higher triglyceride (TG) content (93 ± 3 vs. 67 ± 2 nmol/mg protein in controls, P < 0.05) after 24-h exposure to 1 mM oleate. Furthermore, ACSL1 overexpression produced a 60% increase in cellular LCA-CoA content (160 ± 6 vs. 100 ± 6 nmol/g protein in controls, P < 0.05) and increased [14C]oleate incorporation into TG without significantly altering fatty acid oxidation. In mice, AdACSL1 administration increased ACSL1 mRNA and protein more than fivefold over controls at 4 days postinfection. ACSL1 overexpression caused a twofold increase in TG content in mouse liver (39 ± 4 vs. 20 ± 2 μmol/g wet wt in controls, P < 0.05), and overexpression in rat liver increased [1-14C]palmitate clearance into liver TG. These in vitro and in vivo results suggest a pivotal role for ACSL1 in regulating TG synthesis in liver.
Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability
Authors: Fujita Satoshi , Rasmussen Blake B. , Cadenas Jerson G. , Grady James J. , Volpi Elena
Published: May 2006

Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low (LD, 0.05), intermediate (ID, 0.15), or high (HD, 0.30 mU·min−1·100 ml−1) doses. Insulin was infused locally to induce muscle hyperinsulinemia within the physiological range while minimizing the systemic effects. Protein and amino acid kinetics across the leg were assessed using stable isotopes and muscle biopsies. The LD did not affect phenylalanine delivery to the muscle (−9 ± 18% change over baseline), muscle protein synthesis (16 ± 26%), breakdown, or net balance. The ID increased ( P < 0.05) phenylalanine delivery (+63 ± 38%), muscle protein synthesis (+157 ± 54%), and net protein balance, with no change in breakdown. The HD did not change phenylalanine delivery (+12 ± 11%) or muscle protein synthesis (+9 ± 19%), and reduced muscle protein breakdown (−17 ± 15%), thus improving net muscle protein balance but to a lesser degree than the ID. Changes in muscle protein synthesis were strongly associated with changes in muscle blood flow and phenylalanine delivery and availability. In conclusion, physiological hyperinsulinemia promotes muscle protein synthesis as long as it concomitantly increases muscle blood flow, amino acid delivery and availability.
The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-α in 3T3-L1 adipocytes and is a target for transactivation by PPARγ
Authors: Kim Ji Young , Tillison Kristin , Lee Jun-Ho , Rearick David A. , Smas Cynthia M.
Published: May 2006

The minimal adipose phenotype of hormone-sensitive lipase (HSL)-null mice suggested that other hormonally responsive lipase(s) were present in adipocytes. Recent studies have characterized a new adipose tissue triglyceride lipase, ATGL/PNPLA2/destnutrin/iPLA2ζ/TTS2.2 (ATGL). We had previously cloned a novel adipose-enriched transcript by differential screening and recently determined its identity with murine ATGL. We report here on the regulation of ATGL by TNF-α and insulin in 3T3-L1 adipocytes and identify ATGL as a target for transcriptional activation by the key adipogenic transcription factor PPARγ. Insulin at 100 nM resulted in a marked decrease in ATGL transcript that was effectively blocked by inhibitors for PI 3-kinase and p70 ribosomal protein S6 kinase. TNF-α treatment decreased ATGL transcript in a time-dependent manner that paralleled TNF-α downregulation of PPARγ with a maximal decrease noted by 6 h. TNF-α effects on ATGL were attenuated by pretreatment with PD-98059, LY-294002, or rapamycin, suggesting involvement of the p44/42 MAP kinase, PI 3-kinase, and p70 ribosomal protein S6 kinase signals. To study transcriptional regulation of ATGL, we cloned 2,979 bp of the murine ATGL 5′-flanking region. Compared with promoterless pGL2-Basic, the −2979/+21 ATGL luciferase construct demonstrated 120- and 40-fold increases in activity in white and brown adipocytes, respectively. Luciferase reporter activities for a series of eight ATGL promoter deletions revealed that the −928/+21, −1738/+21, −1979/+21, and −2979/+21 constructs were transactivated by PPARγ. Our findings identify the novel lipase ATGL to be a target gene for TNF-α and insulin action in adipocytes and reveal that it is subject to transcriptional control by PPARγ-mediated signals.
Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats
Authors: Kinman Renée P. , Kasumov Takhar , Jobbins Kathryn A. , Thomas Katherine R. , Adams Jillian E. , Brunengraber Lisa N. , Kutz Gerd , Brewer Wolf-Ulrich , Roe Charles R. , Brunengraber Henri
Published: May 2006

A new chronic treatment for inherited disorders of long-chain fatty acid oxidation involves administering up to one-third of dietary calories as triheptanoin, a medium-odd-chain triglyceride (Roe CR, Sweetman L, Roe DS, David F, and Brunengraber H. J Clin Invest 110: 259–269, 2002). Heptanoate and C5-ketone bodies derived from its partial oxidation in liver are precursors of anaplerotic propionyl-CoA in peripheral tissues. It was hypothesized that increasing anaplerosis in peripheral tissues would boost energy production. In the present study, we tested the potential of a triheptanoin emulsion as an intravenous nutrient. Normal rats were infused with triheptanoin intravenously or intraduodenally at up to 40% of caloric requirement. The blood concentration ratio (heptanoate/C5-ketone bodies) was high with intravenous and low with intraduodenal triheptanoin infusion. During intravenous infusion of triheptanoin, lipolysis was stimulated but appeared compensated by fatty acid reesterification. During intraduodenal infusion of triheptanoin, lipolysis was not stimulated. Our data support the hypothesis that intravenous triheptanoin could be used to treat decompensated patients with long-chain fatty acid oxidation disorders.
Lipid metabolism and secretory function of porcine intramuscular adipocytes compared with subcutaneous and perirenal adipocytes
Authors: Gardan Delphine , Gondret Florence , Louveau Isabelle
Published: May 2006

The function of adipocytes interspersed between myofiber fasciculi in skeletal muscle physiology and physiopathology is poorly documented. Because regional differences in adipocyte features have been reported in various species, we hypothesized that lipid metabolism and secretory function of intramuscular (IM) adipocytes differ from that of nonmuscular adipocytes. In the present study, adipocytes isolated from trapezius muscle were compared with subcutaneous and perirenal adipocytes in growing pigs. Between 80 and 210 days of age, gene expressions and/or activities of enzymes involved in lipogenesis or lipolysis were much lower ( P < 0.05) in adipocytes isolated from muscle than in those from other locations. Insulin-induced lipogenesis and lipolytic efficiency after catecholamine addition were also the lowest ( P < 0.05) in IM adipocytes. In these cells, the age-related increase (+300%) in the ratio of mRNA levels of fatty acid synthase to hormone-sensitive lipase paralleled the enlargement of adipocyte diameters (+70%, P < 0.05) and the increase in lipid content in muscle (+135%, P < 0.05) during growth. Expressions of genes coding for leptin, adiponectin, and IGF-I, as well as for various hormonal receptors, were lower ( P < 0.05) in IM adipocytes than in other adipocytes, whereas levels of TNF-α mRNA did not differ between sites. Interestingly, IGF-II mRNA levels were higher ( P < 0.05) in IM adipocytes than in other adipocytes. These data support the view that IM fat is not just an ectopic extension of other fat locations but displays specific biological features during growth.
Inhibition of calpain results in impaired contraction-stimulated GLUT4 translocation in skeletal muscle
Authors: Otani Kenichi , Polonsky Kenneth S. , Holloszy John O. , Han Dong-Ho
Published: May 2006

It was previously found that transgenic mice that overexpress the calpain inhibitor calpastatin (CsTg) have an ∼3-fold increase in GLUT4 protein in their skeletal muscles. Despite the increase in GLUT4, which appears to be due to inhibition of its proteolysis by calpain, insulin-stimulated glucose transport is not increased in CsTg muscles. PKB (Akt) protein level is reduced ∼60% in CsTg muscles, suggesting a possible mechanism for the relative insulin resistance. Muscle contractions stimulate glucose transport by a mechanism that is independent of insulin signaling. The purpose of this study was to test the hypothesis that the threefold increase in GLUT4 in CsTg would result in a large increase in contraction-stimulated glucose transport. CAMKII and AMPK mediate steps in the contraction-stimulated pathway. The protein levels of AMPK and CAMKII were increased three- to fourfold in CsTg muscles, suggesting that these proteins are also calpain substrates. Despite the large increases in GLUT4, AMPK, and CAMKII, contraction-stimulated GLUT4 translocation and glucose transport were not increased above wild-type values. These findings suggest that inhibition of calpain results in impairment of a step in the GLUT4 translocation process downstream of the insulin- and contraction-signaling pathways. They also provide evidence that CAMKII and AMPK are calpain substrates.
Endothelin and nitric oxide mediate adaptation of the cortical collecting duct to metabolic acidosis
Authors: Tsuruoka Shuichi , Watanabe Seiji , Purkerson Jeffrey M. , Fujimura Akio , Schwartz George J.
Published: May 2006

Endothelin (ET) and nitric oxide (NO) modulate ion transport in the kidney. In this study, we defined the function of ET receptor subtypes and the NO guanylate cyclase signaling pathway in mediating the adaptation of the rabbit cortical collecting duct (CCD) to metabolic acidosis. CCDs were perfused in vitro and incubated for 3 h at pH 6.8, and bicarbonate transport or cell pH was measured before and after acid incubation. Luminal chloride was reversibly removed to isolate H+and HCO3−secretory fluxes and to raise the pH of β-intercalated cells. Acid incubation caused reversal of polarity of net HCO3−transport from secretion to absorption, comprised of a 40% increase in H+secretion and a 75% decrease in HCO3−secretion. The ETBreceptor antagonist BQ-788, as well as the NO synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), attenuated the adaptive decrease in HCO3−secretion by 40%, but only BQ-788 inhibited the adaptive increase in H+secretion. There was no effect of inactive d-NAME or the ETAreceptor antagonist BQ-123. Both BQ-788 and l-NAME inhibited the acid-induced inactivation (endocytosis) of the apical Cl−/HCO3−exchanger. The guanylate cyclase inhibitor LY-83583 and cGMP-dependent protein kinase inhibitor KT-5823 affected HCO3−transport similarly to l-NAME. These data indicate that signaling via the ETBreceptor regulates the adaptation of the CCD to metabolic acidosis and that the NO guanylate cyclase component of ETBreceptor signaling mediates downregulation of Cl−/HCO3−exchange and HCO3−secretion.
Regulation of ecto-5′-nucleotidase by NaCl and nitric oxide: potential roles in tubuloglomerular feedback and adaptation
Authors: Satriano Joseph , Wead Lucinda , Cardus Anna , Deng Aihua , Boss Gerry R. , Thomson Scott C. , Blantz Roland C.
Published: May 2006

The tubuloglomerular feedback (TGF) system serves to establish an appropriate balance between tubular reabsorption and glomerular filtration rate (GFR). High salt at the macula densa activates TGF to decrease GFR. Effector molecules for the TGF signal include ATP and adenosine. Over time, the GFR will adapt by increasing even if a high salt concentration persists. A potential modulator of this TGF adaptation is nitric oxide synthase-1-derived nitric oxide (NO). In isolated glomerular preparations, we developed a system for evaluating the effects of changing dietary salt on ecto-5′-nucleotidase (ecto-5′-NT) activity, the final enzyme in the conversion of ATP to adenosine. We found observable ecto-5′-NT activity in isolated glomeruli and that this activity can be regulated by dietary salt, with high salt increasing activity. Conversely, NO decreases ecto-5′-NT activity in glomerular preparations. Moreover, NO inhibition of ecto-5′-NT activity is suppressed in the presence of dithiothreitol, suggesting nitrosylation as a reversible, oxidative stress-sensitive mechanism. The salt-induced activation of ecto-5′-NT correlates with high salt resetting of TGF. NO inhibition of enzymatic activity could be part of the adaptive phase.
Selective upregulation of the ADP-ribosyl cyclases CD38 and CD157 by TNF but not by RANK-L reveals differences in downstream signaling
Authors: Iqbal Jameel , Kumar Kevin , Sun Li , Zaidi Mone
Published: May 2006

In macrophages and osteoclast precursors, the cytokines TNF and RANK-L induce similar downstream pathways and share some of the same adaptor molecules. However, despite these similarities, no defined signaling schematic has emerged to show how each cytokine favors particular pathways. In this report, we investigate whether TNF and RANK-L differentially regulate ADP-ribosyl cyclases-enzymes that are unique in being crucial for immunological function yet detrimental to osteoclastogenesis. TNF but not RANK-L led to the sustained upregulation of both CD38 and CD157 as demonstrated by real-time PCR and flow cytometry. Further investigation demonstrated that this upregulation was a result of continuous, direct TNF signaling and involved JNK, and more critically PKC and NF-κB. Using this approach allowed us to highlight the relative importance of the PKC, NF-κB, and JNK pathways in actualizing proper outcomes of TNF signaling. Albeit speculative, we believe that differences between TNF- and RANK-l-induced activation of downstream signaling pathways, in particular PKC, are crucial for determining whether progenitor cells become geared for immunity or bone resorption.
Thiamin uptake by the human-derived renal epithelial (HEK-293) cells: cellular and molecular mechanisms
Authors: Ashokkumar Balasubramaniem , Vaziri Nosratola D. , Said Hamid M.
Published: May 2006

Thiamin (vitamin B1) is essential for normal cellular functions. The kidneys play a critical role in regulating body thiamin homeostasis, by salvaging the vitamin via reabsorption from the glomerular filtrate, but little is known about the mechanism(s) and regulation of thiamin transport in the human renal epithelia at cellular and molecular levels. Using the human-derived renal epithelial HEK-293 cells as a model, we have addressed these issues. Our results showed [3H]thiamin uptake to be 1) temperature and energy dependent but Na+independent, 2) pH dependent with higher uptake at alkaline/neutral buffer pH compared with acidic pH, 3) saturable as a function of concentration over the nanomolar (apparent Km= 70.0 ± 18.4 nM) and micromolar (apparent Km= 2.66 ± 0.18 μM) ranges, 4) cis-inhibited by unlabeled thiamin and its structural analogs but not by unrelated organic cations, 5) trans-stimulated by unlabeled thiamin, and 6) competitively inhibited by amiloride with an apparent Kiof 0.6 mM. Using a gene-specific small-interference RNAs (siRNAs) approach, human thiamin transporters 1 and 2 (hTHTR-1 and hTHTR-2) were both found to be expressed and contributed toward total carrier-mediated thiamin uptake. Maintaining the cells in thiamin-deficient medium led to a significant ( P < 0.01) and specific upregulation in [3H]thiamin uptake, which was associated with an increase in hTHTR-1 and hTHTR-2 protein and mRNA levels as well as promoter activities. Uptake of thiamin by HEK-293 cells also appeared to be under the regulation of an intracellular Ca2+/calmodulin-mediated pathway. These studies demonstrate for the first time that thiamin uptake by HEK-293 cells is mediated via a specific pH-dependent process, which involves both the hTHTR-1 and hTHTR-2. In addition, the uptake process appears to be under the regulation of an intracellular Ca2+/CaM-mediated pathway and also adaptively upregulated in thiamin deficiency via transcriptional regulatory mechanism(s) that involves both the hTHTR-1 and hTHTR-2.
Characterization of diabetic nephropathy in a transgenic model of hypoinsulinemic diabetes
Authors: Kanetsuna Yukiko , Hirano Keita , Nagata Michio , Gannon Maureen A. , Takahashi Keiko , Harris Raymond C. , Breyer Matthew D. , Takahashi Takamune
Published: May 2006

Genetic mouse models provide a unique opportunity to investigate gene function in the natural course of the disease. Although diabetic nephropathy (DN) in models of type II diabetes has been well characterized, diabetic renal disease in hypoinsulinemic diabetic mice is still incompletely understood. Here, we characterized renal changes in the pdx1PB-HNF6 transgenic mouse that exhibits β-cell dysfunction and nonobese hypoinsulinemic diabetes. Male transgenic mice developed hyperglycemia by the age of 7 wk and survived for over 1 yr without insulin treatment. Diabetes ensued earlier and progressed more severely in the HNF6 males than the females. The HNF6 males exhibited albuminuria as early as 10 wk of age, and the urinary albumin excretion increased with age, exceeding 150 μg/24 h at 11 mo of age. Diabetic males developed renal hypertrophy after 7 wk of age, whereas glomerular hyperfiltration was not observed in the mice. Hypertension and hyperlipidemia were not observed in the diabetic mice. Histological analysis of the HNF6 kidneys displayed diabetic glomerular changes, including glomerular enlargement, diffuse mesangial proliferation and matrix expansion, thickened glomerular basement membrane, and arteriolar hyalinosis. Mesangial matrix accumulation increased with age, resulting in nodular lesions by 44 wk of age. Immunohistochemistry showed accumulation of type IV collagen and TGF-β1 in the mesangial area. No significant immune complex deposition was observed in the HNF6 glomeruli. Thus the HNF6 mouse exhibits diabetic renal changes that parallel the early phase of human DN. The model should facilitate studies of genetic and environmental factors that may affect DN in hypoinsulinemic diabetes.