bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycosylation of the receptor guanylate cyclase C: role in ligand binding and catalytic activity
Authors: GHANEKAR Yashoda , CHANDRASHAKER Akhila , TATU Utpal , VISWESWARIAH Sandhya S.
Published: April 2004

GC-C (guanylate cyclase C) is the receptor for heat-stable enterotoxins, guanylin and uroguanylin peptides. Ligand binding to the extracellular domain of GC-C activates the guanylate cyclase domain leading to accumulation of cGMP. GC-C is expressed as differentially glycosylated forms in HEK-293 cells (human embryonic kidney-293 cells). In the present study, we show that the 145 kDa form of GC-C contains sialic acid and galactose residues and is present on the PM (plasma membrane) of cells, whereas the 130 kDa form is a high mannose form that is resident in the endoplasmic reticulum and serves as the precursor for the PM-associated form. Ligand-binding affinities of the differentially glycosylated forms are similar, indicating that glycosylation of GC-C does not play a role in direct ligand interaction. However, ligand-stimulated guanylate cyclase activity was observed only for the fully mature form of the receptor present on the PM, suggesting that glycosylation had a role to play in imparting a conformation to the receptor that allows ligand stimulation. Treatment of cells at 20 °C led to intracellular accumulation of a mature glycosylated form of GC-C that now showed ligand-stimulated guanylate cyclase activity, indicating that localization of GC-C was not critical for its catalytic activity. To determine if complex glycosylation was required for ligand-stimulated activation of GC-C, the receptor was expressed in HEK-293 cells that were deficient in N-acetylglucosaminyltransferase 1. This minimally glycosylated form of the receptor was expressed on the cell surface and could bind a ligand with an affinity comparable with the 145 kDa form of the receptor. However, this form of the receptor was poorly activated by the ligand. Therefore our studies indicate a novel role for glycosidic modification of GC-C during its biosynthesis, in imparting subtle conformational changes in the receptor that allow for ligand-mediated activation and perhaps regulation of basal activity.
Getting into position: the catalytic mechanisms of protein ubiquitylation
Authors: PASSMORE Lori A. , BARFORD David
Published: April 2004

The role of protein ubiquitylation in the control of diverse cellular pathways has recently gained widespread attention. Ubiquitylation not only directs the targeted destruction of tagged proteins by the 26 S proteasome, but it also modulates protein activities, protein–protein interactions and subcellular localization. An understanding of the components involved in protein ubiquitylation (E1s, E2s and E3s) is essential to understand how specificity and regulation are conferred upon these pathways. Much of what we know about the catalytic mechanisms of protein ubiquitylation comes from structural studies of the proteins involved in this process. Indeed, structures of ubiquitin-activating enzymes (E1s) and ubiquitin-conjugating enzymes (E2s) have provided insight into their mechanistic details. E3s (ubiquitin ligases) contain most of the substrate specificity and regulatory elements required for protein ubiquitylation. Although several E3 structures are available, the specific mechanistic role of E3s is still unclear. This review will discuss the different types of ubiquitin signals and how they are generated. Recent advances in the field of protein ubiquitylation will be examined, including the mechanisms of E1, E2 and E3. In particular, we discuss the complexity of molecular recognition required to impose selectivity on substrate selection and topology of poly-ubiquitin chains.
Cholesterol-dependent partitioning of PtdIns(4,5)P2 into membrane domains by the N-terminal fragment of NAP-22 (neuronal axonal myristoylated membrane protein of 22 kDa)
Authors: EPAND Richard M. , VUONG Phan , YIP Christopher M. , MAEKAWA Shohei , EPAND Raquel F.
Published: April 2004

A myristoylated peptide corresponding to the N-terminus of NAP-22 (neuronal axonal myristoylated membrane protein of 22 kDa) causes the quenching of the fluorescence of BODIPY®-TMR-labelled PtdIns(4,5)P2 in bilayers of 1-palmitoyl-2-oleoyl phosphatidylcholine containing 40 mol% cholesterol and 0.1 mol% BODIPY®–PtdIns(4,5)2. Both fluorescence spectroscopy and total internal reflectance fluorescence microscopy revealed the cholesterol-dependent nature of PtdIns(4,5)P2-enriched membrane-domain formation.
Does physical training increase insulin sensitivity in chronic heart failure patients?
Authors: SABELIS L. W. E. , SENDEN P. J. , TE BOEKHORST B. C. M. , HULZEBOS H. J. , VAN DE WIEL A. , VAN HAEFTEN T. W. , ZONDERLAND M. L. , MOSTERD W. L.
Published: April 2004

To determine the effect of training on insulin sensitivity (IS) and how this relates to peak VO2 (peak oxygen uptake) in CHF (chronic heart failure), 77 CHF patients (New York Heart Association class, II/III; men/women, 59/18; age, 60±9 years; body mass index, 26.7±3.9 kg/m2; left ventricular ejection fraction, 26.9±8.1%; expressed as means±S.D.) participated in the study. Patients were randomly assigned to a training or control group (TrG or CG respectively). Sixty-one patients completed the study. Patients participated in training (combined strength and endurance exercises) four times per week, two times supervised and two times at home. Before and after intervention, anthropometry, IS (euglycaemic hyperinsulinaemic clamp) and peak VO2 (incremental cycle ergometry) were assessed. Intervention did not affect IS significantly, even though IS increased by 20% in TrG and 11% in CG (not significant). Peak VO2 increased as a result of training (6% increase in TrG; 2% decrease in CG; P<0.05). In both groups (TrG and CG), the change in IS correlated positively with the change in peak VO2 (r=0.30, P<0.05). Training resulted in an increase in peak VO2, but not in IS. Whether physical training actually increases IS in CHF patients remains unclear.
Birefringence reduction method for optical polymers by the orientation-inhibition effect of silica particles
Authors: Ohkita Hisanori , Abe Yasuyuki , Kojima Hiroshi , Tagaya Akihiro , Koike Yasuhiro
Published: April 2004

A method for reducing the orientational birefringence of polymers by doping with optically isotropic silica particles is reported. Particles with a diameter of 16 nm were selected and their surface was treated with dimethyldichlorosilane. Doping with 1 wt% of the particles reduced about 15% of the orientational birefringence of polycarbonate and poly(methylmethacrylate) films regardless of the sign and the magnitude of their birefringence. The analysis of the infrared dichroic ratio confirmed an effect in which the particles reduced the orientation of polycarbonate main chains. The effect that caused the reduction of birefringence was named “the orientation-inhibition effect.”
Fundamental limits to detection of low-energy ions using silicon solid-state detectors
Authors: Funsten H. O. , Ritzau S. M. , Harper R. W. , Korde R.
Published: April 2004

Recent advances in solid-state detector (SSD) technology have demonstrated the detection of ions and electrons down to 1 keV. However, ions at keV energies lose a substantial amount of energy ΔN in a SSD through Coulombic interactions with target nuclei rather than through interactions that contribute to the SSD output pulse, whose magnitude is a measure of the ion’s incident energy. Because ΔN depends on the ion species, detector material, and interaction physics, it represents a fundamental limitation of the output pulse magnitude of the detector. Using 100% quantum collection efficiency silicon photodiodes with a thin (40–60 Å) SiO2 passivation layer, we accurately quantify ΔN for incident 1–120 keV ions and, therefore, evaluate the detection limits of keV ions using silicon detectors.
Nondestructive depth profile of the chemical state of ultrathin Al2O3/Si interface
Authors: Lee Jong Cheol , Oh S.-J.
Published: April 2004

We investigated a depth profile of the chemical states of an Al2O3/Si interface using nondestructive photon energy-dependent high-resolution x-ray photoelectron spectroscopy (HRXPS). The Si 2p binding energy, attributed to the oxide interfacial layer (OIL), was found to shift from 102.1 eV to 102.9 eV as the OIL region closer to Al2O3 layer was sampled, while the Al 2p binding energy remains the same. This fact strongly suggests that the chemical state of the interfacial layer is not Al silicate as previously believed. We instead propose from the HRXPS of Al 2p and Si 2p depth-profile studies that the chemical states of the Al2O3/Si interface mainly consist of SiO2 and Si2O3.
Synthesis of uniform GaN quantum dot arrays via electron nanolithography of D2GaN3
Authors: Crozier P. A. , Tolle J. , Kouvetakis J. , Ritter Cole
Published: April 2004

We demonstrate the deposition of periodic arrays of uniformly sized GaN quantum dots onto a SiOx substrate. The dots are deposited using a nanolithography technique based on a combination of electron-beam-induced chemical vapor deposition and single-source molecular hydride chemistries. Under appropriate deposition conditions, we can deposit uniform dots of height 5 nm and full widths at half-maxima of 4 nm. The dot size is controlled by the spatial distribution of secondary electrons leaving the substrate surface. The smallest, most uniform void-free dots are created via nanolithography of molecules adsorbed on the substrate surface.
Impact of dislocations on minority carrier electron and hole lifetimes in GaAs grown on metamorphic SiGe substrates
Authors: Andre C. L. , Boeckl J. J. , Wilt D. M. , Pitera A. J. , Lee M. L. , Fitzgerald E. A. , Keyes B. M. , Ringel S. A.
Published: April 2004

The minority carrier lifetime of electrons (τn) in p-type GaAs double heterostructures grown on GaAs substrates and compositionally graded Ge/Si1−xGex/Si (SiGe) substrates with varying threading dislocation densities (TDDs) were measured at room temperature using time-resolved photoluminescence. The electron lifetimes for homoepitaxial GaAs and GaAs grown on SiGe (TDD∼1×106 cm−2) with a dopant concentration of 2×1017 cm−3 were ∼21 and ∼1.5 ns, respectively. The electron lifetime measured on SiGe was substantially lower than the previously measured minority carrier hole lifetime (τp) of ∼10 ns, for n-type GaAs grown on SiGe substrates with a similar residual TDD and dopant concentration. The reduced lifetime for electrons is a consequence of their higher mobility, which yields an increased sensitivity to the presence of dislocations in GaAs grown on metamorphic buffers. The disparity in dislocation sensitivity for electron and hole recombination has significant implications for metamorphic III-V devices.
High performance of potassium n-doped carbon nanotube field-effect transistors
Authors: Radosavljević M. , Appenzeller J. , Avouris Ph. , Knoch J.
Published: April 2004

We describe a robust technique for the fabrication of high performance vertically scaled n-doped field-effect transistors from large band gap carbon nanotubes. These devices have a tunable threshold voltage in the technologically relevant range (−1.3 V⩽Vth⩽0.5 V) and can carry up to 5–6 μA of current in the on-state. We achieve such performance by exposure to potassium (K) vapor and device annealing in high vacuum. The treatment has a twofold effect to: (i) controllably shift Vth toward negative gate biases via bulk doping of the nanotube (up to about 0.6e−/nm), and (ii) increase the on-current by 1–2 orders of magnitude. This current enhancement is achieved by lowering external device resistance due to more intimate contact between K metal and doped nanotube channel in addition to potential reduction of the Schottky barrier height at the contact.
1 micron wavelength photo- and electroluminescence from a conjugated polymer
Authors: Chen Miaoxiang , Perzon Erik , Andersson Mats R. , Marcinkevicius Saulius , Jönsson S. K. M. , Fahlman Mats , Berggren Magnus
Published: April 2004

We report photo- and electroluminescence from an alternating conjugated polymer consisting of fluorene units and low-band gap donor-acceptor-donor (D–A–D) units. The D–A–D segment includes two electron-donating thiophene rings combined with a thiadiazolo-quinoxaline unit, which is electron withdrawing to its nature. The resulting polymer is conjugated and has a band gap of 1.27 eV. The corresponding electro- and photoluminescence spectra both peak at approximately 1 μm. Light-emitting diodes, based on a single layer of the polymer, demonstrated external quantum efficiencies from 0.03% to 0.05%.
Crossover of thickness dependence of critical current density Jc(T,H) in YBa2Cu3O7−δ thick films
Authors: Li Qiang , Suenaga M. , Ye Z. , Foltyn S. R. , Wang H.
Published: April 2004

Critical current density Jc as a function of temperature T and magnetic field H was studied for high quality YBa2Cu3O7−δ (YBCO) films with thickness d=0.2, 1, and 3 μm by means of magnetization measurements of a circular disk in perpendicular field. We found that the thickness dependence of Jc(H) for the YBCO thick films crossovers at high fields for T>50 K, where the 0.2-μm-thick film carries significantly lower Jc(H) than the 3-μm-thick film at high fields, even though the zero- or low-field Jc for the 0.2-μm-thick film is more than twice the value for the 3-μm-thick film.
Spin relaxation dynamics in highly uniform InAs quantum dots
Authors: Tackeuchi A. , Ohtsubo R. , Yamaguchi K. , Murayama M. , Kitamura T. , Kuroda T. , Takagahara T.
Published: April 2004

We have investigated carrier spin dynamics in highly uniform self-assembled InAs quantum dots. The highly uniform quantum dots allowed us to observe the spin dynamics in the ground state and that in the second state separately, without the disturbance of inhomogeneous broadening. The spin relaxation times in the ground state and the second state were measured to be 1.0 and 0.6 ns, respectively. Our measurements reveal the absence of the carrier density dependence of the spin relaxation time. The measured spin relaxation time decreases rapidly from 1.1 ns at 10 K to 200 ps at 130 K. This large change in the spin relaxation time is well explained in terms of the mechanism of acoustic phonon emission.
Cyclic surface morphology change related to Li ion movement in Li secondary microbattery embedded in Si substrate: Atomic force microscopy studies
Authors: Kushida K. , Kuriyama K.
Published: April 2004

Surface morphology and charge/discharge characteristic in a 5×5 μm2 area of an all-solid-state Li secondary battery (Al/Li/SiO2–15 at. %P2O5/LiMn2O4/polycrystalline silicon) embedded in a Si substrate are simultaneously observed by atomic force microscopy with a conductive probe. The battery area of 5×5 μm2 shows charge/discharge behavior corresponding to the movement of ∼2.9×1010 Li+ ions/μm2, reflecting the cyclic movement of Li+ ions. The Al electrode consisting of scale-shaped grains of 0.1–1.5 μm in size rises by ∼30 nm during the first charge operation. The surface of the Al electrode shows a cyclic change from scaly to wrinkled structures with the charge/discharge operations, indicating the drawing of the excess Li in the anode into the glassy electrolyte. These results are promising for the realization of a micrometer-sized battery.
Coherent terahertz emission from ferromagnetic films excited by femtosecond laser pulses
Authors: Beaurepaire E. , Turner G. M. , Harrel S. M. , Beard M. C. , Bigot J.-Y. , Schmuttenmaer C. A.
Published: April 2004

It is shown that the laser induced ultrafast demagnetization of ferromagnetic films results in the emission of a terahertz electromagnetic pulse. This emission has been detected from Ni films using free-space electro-optic sampling. The radiated electric field E(t) is explained by Maxwell equations (radiation from a time dependent magnetic dipole), and is expected to be proportional to the second time derivative of the magnetization d2M/dt2, as measured in the far field. This technique opens appealing perspectives in the context of measuring and understanding the ultrafast spin dynamics as well as the interaction of electrons (both charge and spin) with electromagnetic fields.
Perpendicular exchange bias in antiferromagnetic-ferromagnetic nanostructures
Authors: Sort J. , Dieny B. , Fraune M. , Koenig C. , Lunnebach F. , Beschoten B. , Güntherodt G.
Published: April 2004

Exchange bias effects have been induced along the perpendicular-to-film direction in nanostructures prepared by electron beam lithography, consisting of a ferromagnetic [Pt/Co] multilayer exchange coupled to an antiferromagnet (FeMn). As a general trend, the exchange bias field and the blocking temperature decrease, whereas the coercivity increases, as the size of the nanostructures is reduced.
Double-well model of dielectric relaxation current
Authors: Jameson John R. , Harrison Walter , Griffin P. B. , Plummer J. D.
Published: April 2004

We show that a straightforward account of dielectric relaxation current in glasses follows from a semiclassical treatment of the double-well model [P. W. Anderson, B. I. Halperin, and C. M. Varma, Philos. Mag. 25, 1 (1972) and W. A. Phillips, J. Low Temp. Phys. 7, 351 (1972)] explaining the linear specific heat of glasses at low temperature. The current is obtained from the field-induced tunneling of the glass between the minima of its potential energy surface, and is found to have the experimentally observed linear dependence on field and inverse dependence on time. The effects of temperature and prior biases are briefly discussed, as well as the relation of the model to the theory of charge trapping. No dielectric relaxation is expected in a perfect insulating crystal, raising the important technological question of how perfect high-k dielectrics like HfO2 and ZrO2 must be in order to serve as gate dielectrics in transistors.
Field-emission properties of quasi-one-dimensional NbOx crystals
Authors: Žumer Marko , Nemanič Vincenc , Zajec Bojan , Remškar Maja , Mrzel Aleš , Mihailovič Dragan
Published: April 2004

The field-emission (FE) properties of quasi-one-dimensional NbOx crystals are reported for the single needle geometry. Relatively stable FE currents in excess of 1 μA were measured after a careful conditioning in vacuum of 10−7 mbar. In all our experiments, the FE current originating from a few sites prevailed over the entire current range. This can be confirmed at least in the current range where the emission pattern could be observed on a high-resolution luminescent screen.
Highly processable bulk metallic glass-forming alloys in the Pt–Co–Ni–Cu–P system
Authors: Schroers Jan , Johnson William L.
Published: April 2004

Highly processable bulk metallic glass alloys in the Pt–Co–Ni–Cu–P system were discovered. The alloys show low liquidus temperature below 900 K, excellent processability with low critical cooling rate reflecting in maximum casting thicknesses in quartz tubes of up to 20 mm, and a large supercooled liquid region. The Pt57.5Cu14.7Ni5.3P22.5 composition has a liquidus temperature of 795 K, a glass transition temperature of 508 K with a supercooled liquid region of 98 K. For medical and jewelry applications a Ni-free alloy, Pt60Cu16Co2P22 was discovered with a liquidus temperature of 881 K, a glass transition temperature of 506 K, and a supercooled liquid region of 63 K. Glass formation was observed in a wider composition range. Vickers hardness of these alloys is in the 400 Hv range. The alloys can be processed in the supercooled liquid region in air without any measurable oxidation. In this region, a large processing window is available in which the material does not embrittle. Embrittlement in these alloys is correlated with crystallization. It can be avoided as long as substantial crystallization does not take place during isothermal processing in the supercooled liquid region. Also, liquid processing can be performed in air when flux with B2O3.
Upper critical fields of powder-in-tube-processed MgB2/Fe tape conductors
Authors: Kumakura H. , Kitaguchi H. , Matsumoto A. , Hatakeyama H.
Published: April 2004

We measured the upper critical field, Bc2, of pure and SiC-added MgB2/Fe tapes prepared by the powder-in-tube process. We found that the Bc2 of the MgB2 tapes was much higher than the Bc2 of MgB2 single crystals. At 4.2 K, the Bc2 of the 10 mol % SiC-added MgB2 tape reached 22.5 T. This Bc2 was almost equal to the Bc2 of a conventional bronze-processed Nb3Sn conductor. At 20 K, the Bc2 of the 5 mol % SiC-added tape was around 10 T, which was comparable to the Bc2 of commercial Nb–Ti at 4.2 K. These results indicate that powder-in-tube-processed MgB2 tape is promising not only for high-field applications but also for applications at 20 K with a convenient cryo-cooler.
Electron energy-loss spectroscopy analysis of the electronic structure of nitrided Hf silicate films
Authors: Ikarashi Nobuyuki , Miyamura Makoto , Masuzaki Koji , Tatsumi Toru
Published: April 2004

We have shown, using electron energy-loss spectroscopy, that incorporating N into a Hf silicate film reduces the band gap. We also experimentally clarified that the Hf atoms in the film are coordinated by N atoms, and we used ab initio electronic structure calculations to show that the Hf–N coordination can be a cause of the decrease in the band gap. Therefore, when a Hf silicate film is used as a gate dielectric in a metal-oxide-semiconductor field-effect transistor, N incorporation can affect the gate leakage current because the decrease in the band gap lowers the band offsets of the dielectric on Si.
Organic light-emitting devices with laminated top contacts
Authors: Bernards Daniel A. , Biegala Tomasz , Samuels Zachary A. , Slinker Jason D. , Malliaras George G. , Flores-Torres Samuel , Abruña Héctor D. , Rogers John A.
Published: April 2004

We demonstrate the fabrication of organic light-emitting devices based on a ruthenium complex with indium tin oxide anodes and laminated Au cathodes. Light emission was uniform over the whole device area, indicating a high-quality mechanical and electrical contact. The devices showed no rectification, indicating that the laminated contact was ohmic and caused no damage to the ruthenium complex. Comparison with devices using evaporated Au cathodes confirmed the quality of the lamination process.
Formation of CdSe quantum dots on homoepitaxial ZnSe
Authors: Sadofev S. , Blumstengel S. , Henneberger F.
Published: April 2004

CdSe quantum dots were prepared by molecular beam epitaxy on homoepitaxially grown ZnSe (001) via thermally activated reorganization of an initially two-dimensional film. In spite of the difficulties related to the ZnSe substrate treatment prior to the epitaxial growth, atomically smooth sample surfaces could be achieved with increasing growth time and layer-by-layer growth was realized. The photoluminescence quantum yield of the quantum dots grown on homoepitaxial ZnSe is only slightly reduced in comparison to the standard epitaxy using GaAs as substrate. Distinct single-dot features were identified using a micro-optical setup.
Field-induced nonequilibrium electron distribution and electron transport in a high-quality InN thin film grown on GaN
Authors: Liang W. , Tsen K. T. , Ferry D. K. , Lu Hai , Schaff William J.
Published: April 2004

Nonequilibrium electron transport in a high-quality, single-crystal, wurtzite structure InN thin film grown on GaN has been investigated by picosecond Raman spectroscopy. Our experimental results show that an electron drift velocity as high as (5.0±0.5)×107 cm/s can be achieved at T=300 K. The experimental results have been compared with ensemble Monte Carlo simulations and good agreement is obtained. From the comparison, we have also deduced that the built-in electric-field intensity inside our InN thin-film system is about 75 kV/cm.
Mg–Ni–H films as selective coatings: Tunable reflectance by layered hydrogenation
Authors: van Mechelen J. L. M. , Noheda B. , Lohstroh W. , Westerwaal R. J. , Rector J. H. , Dam B. , Griessen R.
Published: April 2004

Unlike other switchable mirrors, Mg2NiHx films show large changes in reflection that yield very low reflectance (high absorptance) at different hydrogen contents, far before reaching the semiconducting state. The resulting reflectance patterns are of interference origin, due to a self-organized layered hydrogenation mechanism that starts at the substrate interface, and can therefore be tuned by varying the film thickness. This tunability, together with the high absorptance contrast observed between the solar and the thermal energies, strongly suggests the use of these films in smart coatings for solar applications.
Main Group Pyrazolates—the X-Ray Structures of [Al(η2-But2pz)3], [SnMe3(η1-Ph2pz)] and [GePh3(η1-But2pz)] (R2pz = 3,5-Disubstituted Pyrazolate)
Authors: Deacon Glen B. , Delbridge Ewan E. , Forsyth Craig M. , Junk Peter C. , Skelton Brian W. , White Allan H.
Published: April 2004

From metathesis reactions between AlCl3,
SnMe3Cl, or GePh3Br and the appropriate potassium
3,5-disubstituted pyrazolate [K(R2pz)] the
complexes [Al(Bu t
2pz)3],
[SnMe3(Ph2pz)],
[SnMe3(Bu t
2pz)], and [GePh3(Bu
t 2pz)] have been obtained.
The X-ray structure of [Al(Bu t
2pz)3] shows the complex to
be monomeric with η2
-pyrazolate groups, in a quasi-trigonal prismatic array: the first monomeric
homoleptic tris(pyrazolato) complex of any element. X-Ray structures of
[SnMe3(Ph2pz)] and
[GePh3(Bu t
2pz)] reveal mononuclear species with distorted
tetrahedral stereochemistries and
η1 -pyrazolate groups.
Comparisons of spectroscopic data between
[SnMe3(Ph2pz)] and
[SnMe3(Bu t
2pz)] suggest the latter is also four-coordinate
with an η1 -Bu
t 2pz
ligand.
High-density lipoprotein and apolipoprotein AI increase endothelial NO synthase activity by protein association and multisite phosphorylation
Authors: Drew Brian G. , Fidge Noel H. , Gallon-Beaumier Gabrielle , Kemp Bruce E. , Kingwell Bronwyn A.
Published: April 2004

NO propagates a number of antiatherogenic effects in the endothelium, and diminished availability has been associated with vascular disease. Recently it has been reported that phosphorylation of endothelial NO synthase (eNOS) at Ser-1179 is required to increase activity in response to stimuli, including high-density lipoprotein (HDL). The current study was undertaken to further examine the mechanism by which HDL activates eNOS and to specifically determine the role of the major apolipoprotein of HDL, apolipoprotein AI (ApoAI). Phosphorylation of eNOS residues Ser-116, Ser-617, Ser-635, Ser-1179, and Thr-497 after incubation with ApoAI and HDL was examined. There were significant increases in phosphorylation at Ser-116 in response to both HDL and ApoAI and similar magnitudes of dephosphorylation at Thr-497. Ser-1179 phosphorylation increased transiently but returned to basal level after 2.5 min. Data demonstrating activation of AMP activated protein kinase (AMPK) during HDL and ApoAI incubation suggests that AMPK may play a role in activation of eNOS. NO release in response to HDL and ApoAI stimulation in endothelial cells paralleled the time frames of phosphorylation, suggesting a causal relationship. Furthermore, ApoAI was found to associate with eNOS in endothelial cells and bind transfected eNOS in Chinese hamster ovary cells, whereas confocal data demonstrates colocalization of ApoAI and eNOS in the perinuclear region, suggesting a protein–protein interaction. Collectively, the results indicate that HDL and ApoAI increase eNOS activity by multisite phosphorylation changes, involving AMPK activation after protein association between ApoAI and eNOS.
Gram-positive bacteria are a major reservoir of Class 1 antibiotic resistance integrons in poultry litter
Authors: Nandi Sobhan , Maurer John J. , Hofacre Charles , Summers Anne O.
Published: April 2004

Reversing the spread of antibiotic multiresistant bacteria is hampered by ignorance of the natural history of resistance genes, the mobile elements carrying them, and the bacterial hosts harboring them. Using traditional cultivation and cultivation-independent molecular techniques, we quantified antibiotic resistance genes and mobile elements called integrons in poultry house litter from commercial poultry farms. Unexpectedly, the major reservoir for Class 1 integrons in poultry litter is not their previously identified hosts, Gram-negative
Enterobacteriaceae
such as
Escherichia coli
. Rather, integrons and associated resistance genes abound in several genera of Gram-positive bacteria that constitute >85% of the litter community compared with
Enterobacteriaceae
that comprise <2% of this ecosystem. This finding warrants reexamination of our assumptions about the persistence and spread of antibiotic resistance genes.
Crystal structure of
Clostridium botulinum
neurotoxin protease in a product-bound state: Evidence for noncanonical zinc protease activity
Authors: Segelke Brent , Knapp Mark , Kadkhodayan Saloumeh , Balhorn Rod , Rupp Bernhard
Published: April 2004

Clostridium botulinum
neurotoxins (BoNTs), the most potent toxins known, disrupt neurotransmission through proteolysis of proteins involved in neuroexocytosis. The light chains of BoNTs are unique zinc proteases that have stringent substrate specificity and require exceptionally long substrates. We have determined the crystal structure of the protease domain from BoNT serotype A (BoNT/A). The structure reveals a homodimer in a product-bound state, with loop F242–V257 from each monomer deeply buried in its partner's catalytic site. The loop, which acts as a substrate, is oriented in reverse of the canonical direction for other zinc proteases. The Y249–Y250 peptide bond of the substrate loop is hydrolyzed, leaving the Y249 product carboxylate coordinated to the catalytic zinc. From the crystal structure of the BoNT/A protease, detailed models of noncanonical binding and proteolysis can be derived which we propose are also consistent with BoNT/A binding and proteolysis of natural substrate synaptosome-associated protein of 25 kDa (SNAP-25). The proposed BoNT/A substrate-binding mode and catalytic mechanism are markedly different from those previously proposed for the BoNT serotype B.
Three replication origins in
Sulfolobus
species: Synchronous initiation of chromosome replication and asynchronous termination
Authors: Lundgren Magnus , Andersson Anders , Chen Lanming , Nilsson Peter , Bernander Rolf
Published: April 2004

Chromosome replication origins were mapped
in vivo
in the two hyperthermophilic archaea,
Sulfolobus acidocaldarius
and
Sulfolobus solfataricus
, by using microarray-based marker frequency analysis. Bidirectional replication was found to be initiated in near synchrony from three separate sites in both organisms. Two of the three replication origins in each species were located in the vicinity of a
cdc6
/
orc1
replication initiation gene, whereas no known replication-associated gene could be identified near the third origin in either organism. In contrast to initiation, replication termination occurred asynchronously, such that certain replication forks continued to progress for >40 min after the others had terminated. In each species, all replication forks advanced at similar DNA polymerization rates; this was found to be an order of magnitude below that displayed by
Escherichia coli
and thus closer to eukaryotic elongation rates. In
S. acidocaldarius
, a region containing short regularly spaced repeats was found to hybridize aberrantly, as compared to the rest of the chromosome, raising the possibility of a centromere-like function.
Poly(A)+ RNAs roam the cell nucleus and pass through speckle domains in transcriptionally active and inactive cells
Authors: Molenaar Chris , Abdulle Abadir , Gena Aarti , Tanke Hans J. , Dirks Roeland W.
Published: April 2004

Many of the protein factors that play a role in nuclear export of mRNAs have been identified, but still little is known about how mRNAs are transported through the cell nucleus and which nuclear compartments are involved in mRNA transport. Using fluorescent 2'O-methyl oligoribonucleotide probes, we investigated the mobility of poly(A)+ RNA in the nucleoplasm and in nuclear speckles of U2OS cells. Quantitative analysis of diffusion using photobleaching techniques revealed that the majority of poly(A)+ RNA move throughout the nucleus, including in and out of speckles (also called SC-35 domains), which are enriched for splicing factors. Interestingly, in the presence of the transcription inhibitor 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole, the association of poly(A)+ RNA with speckles remained dynamic. Our results show that RNA movement is energy dependent and that the proportion of nuclear poly(A)+ RNA that resides in speckles is a dynamic population that transiently interacts with speckles independent of the transcriptional status of the cell. Rather than the poly(A)+ RNA within speckles serving a stable structural role, our findings support the suggestion of a more active role of these regions in nuclear RNA metabolism and/or transport.
Sequential exocytosis of insulin granules is associated with redistribution of SNAP25
Authors: Takahashi Noriko , Hatakeyama Hiroyasu , Okado Haruo , Miwa Akiko , Kishimoto Takuya , Kojima Tatsuya , Abe Teruo , Kasai Haruo
Published: April 2004

We have investigated sequential exocytosis in β cells of intact pancreatic islets with the use of two-photon excitation imaging of a polar fluorescent tracer, sulforhodamine B, and a fusion protein comprising enhanced cyan fluorescent protein (ECFP) and the SNARE protein SNAP25 (synaptosome-associated protein of 25 kD) transfected with an adenoviral vector. Sequential exocytosis was found to account for <10% of exocytic events in β cells stimulated either with glucose under various conditions or by photolysis of a caged-Ca2+ compound. Multigranular exocytosis, in which granule-to-granule fusion occurs before exocytosis, was rarely found. We detected redistribution of ECFP-SNAP25 from the plasma membrane into the membrane of the fused granule occurred in a large proportion (54%) of sequential exocytic events but in only a small fraction (5%) of solitary fusion events. Removal of cholesterol in the plasma membrane by methyl-β-cyclodextrin facilitated both redistribution of ECFP-SNAP25 and sequential exocytosis by threefold. These observations support the hypothesis that SNAP25 is a plasma membrane factor that is responsible for sequential exocytosis.
Regulation of Sodium Channel Function by Bilayer Elasticity
Authors: Lundbæk Jens A. , Birn Pia , Hansen Anker J. , Søgaard Rikke , Nielsen Claus , Girshman Jeffrey , Bruno Michael J. , Tape Sonya E. , Egebjerg Jan , Greathouse Denise V. , Mattice Gwendolyn L. , Koeppe Roger E. , Andersen Olaf S.
Published: April 2004

Membrane proteins are regulated by the lipid bilayer composition. Specific lipid–protein interactions rarely are involved, which suggests that the regulation is due to changes in some general bilayer property (or properties). The hydrophobic coupling between a membrane-spanning protein and the surrounding bilayer means that protein conformational changes may be associated with a reversible, local bilayer deformation. Lipid bilayers are elastic bodies, and the energetic cost of the bilayer deformation contributes to the total energetic cost of the protein conformational change. The energetics and kinetics of the protein conformational changes therefore will be regulated by the bilayer elasticity, which is determined by the lipid composition. This hydrophobic coupling mechanism has been studied extensively in gramicidin channels, where the channel–bilayer hydrophobic interactions link a “conformational” change (the monomer↔dimer transition) to an elastic bilayer deformation. Gramicidin channels thus are regulated by the lipid bilayer elastic properties (thickness, monolayer equilibrium curvature, and compression and bending moduli). To investigate whether this hydrophobic coupling mechanism could be a general mechanism regulating membrane protein function, we examined whether voltage-dependent skeletal-muscle sodium channels, expressed in HEK293 cells, are regulated by bilayer elasticity, as monitored using gramicidin A (gA) channels. Nonphysiological amphiphiles (β-octyl-glucoside, Genapol X-100, Triton X-100, and reduced Triton X-100) that make lipid bilayers less “stiff”, as measured using gA channels, shift the voltage dependence of sodium channel inactivation toward more hyperpolarized potentials. At low amphiphile concentration, the magnitude of the shift is linearly correlated to the change in gA channel lifetime. Cholesterol-depletion, which also reduces bilayer stiffness, causes a similar shift in sodium channel inactivation. These results provide strong support for the notion that bilayer–protein hydrophobic coupling allows the bilayer elastic properties to regulate membrane protein function.
Existence of local sufficiently smooth solutions to the complex Monge-Ampère equation
Authors: Kallel-Jallouli Saoussen
Published: April 2004

We prove theC∞C^{\infty }local solvability of thenn-dimensional complex Monge-Ampère equationdet(uij¯)=f(z,u,∇u)\det \left ( u_{i\overline {j}}\right ) =f\left ( z,u,\nabla u\right ),f≥0f\geq 0, in a neighborhood of any pointz0z_{0}wheref(z0)=0f\left ( z_{0}\right ) =0.
Trees, parking functions, syzygies, and deformations of monomial ideals
Authors: Postnikov Alexander , Shapiro Boris
Published: April 2004

For a graph

G
G

, we construct two algebras whose dimensions are both equal to the number of spanning trees of

G
G

. One of these algebras is the quotient of the polynomial ring modulo certain monomial ideal, while the other is the quotient of the polynomial ring modulo certain powers of linear forms. We describe the set of monomials that forms a linear basis in each of these two algebras. The basis elements correspond to

G
G

-parking functions that naturally came up in the abelian sandpile model. These ideals are instances of the general class of monotone monomial ideals and their deformations. We show that the Hilbert series of a monotone monomial ideal is always bounded by the Hilbert series of its deformation. Then we define an even more general class of monomial ideals associated with posets and construct free resolutions for these ideals. In some cases these resolutions coincide with Scarf resolutions. We prove several formulas for Hilbert series of monotone monomial ideals and investigate when they are equal to Hilbert series of deformations. In the appendix we discuss the abelian sandpile model.
A case study of local food and its routes to market in the UK
Authors: Jones Peter , Comfort Daphne , Hillier David
Published: April 2004

Consumers within the UK have access to a wide variety of international foodstuffs and cuisines but there is also a growing interest in local food. This case study explores what is meant by local food, outlines some of the benefits claimed for, and the problems seen to be associated with, food that is produced and consumed locally and discusses some of the routes to market for local food.
Collecting comic books for an academic library
Authors: Matz Chris
Published: April 2004

Comic books are finally being recognized as a scholarly medium in literature, art, history, popular culture, and many other fields of study. Blanket disapproval of comic books, however, continues in all but a few academic libraries. Librarians do face philosophical and practical challenges to acquiring comic books, but it is both possible and desirable to do so. Valuable selection tools and Internet resources are examined, along with annotations of significant comic book creators.
A new detergent‐free dry‐cleaning system
Authors: Sawa Kohei , Rodriguez Carlos , Aramaki Kenji , Kunieda Hironobu
Published: April 2004

The performance of a new detergent‐free dry cleaning machine has been investigated and compared to conventional machines. The new machine includes a highly efficient system for solvent purification, and effectively cleans wool, cotton and synthetic fibers without the need of detergent. Its performance is similar or in some cases better than the conventional machines, which contaminate the clothes with detergent. Since detergent is not needed and solvent is efficiently used in the new machine, environmental impacts and operation costs are reduced, and the negative side effects on the properties of clothes are eliminated.
Integrating value education and sustainable development into a Dutch university curriculum
Authors: Muijen Heidi
Published: April 2004

Despite the mainstream technological approach of science in academic curricula, with its focus on specialisation, the Dutch history of higher education is an interesting example of an alternative development. The Vrije Universiteit of Amsterdam has declared in its mission statement a pedagogical ideal of “broad academic education”, oriented towards educating students to become “morally responsible and reflective scientists and professionals”. This paper describes a pilot study focusing on organisational dynamics, learning processes involved in value education, and the question of how a philosophical/ethical perspective on sustainability can be integrated into the curriculum. A critical evaluation of this pilot study suggests that students need more insight into the status of values as different from empirical facts.
An environmental management qualification through distance education
Authors: Pretorius Rudi W.
Published: April 2004

The department of geography and environmental studies of the University of South Africa recently played a pivotal role in implementing an inter‐ and multidisciplinary undergraduate programme in environmental management. This programme prepares students for entry‐level occupations, and equips them with the knowledge, skills and values needed to contribute to sustainable development. Both BA and BSc students are catered for, which contributes to the broadening of undergraduate education. This programme is unique because of its inclusion at undergraduate level and because it is offered through distance education. The teaching approach acknowledges that the causes of environmental problems are not simple, and are rooted in the nature of political, social and economic systems. It acknowledges that the solutions to environmental problems are equally complex, requiring not only specialist inputs, but also value and structural shifts. In line with the latest trends in education, a student‐activating approach is followed, with emphasis on real case studies, the flexible application of knowledge, and formative and integrated assessment. An overview is given of the experience that has been gained through designing and implementing this programme. This experience may serve to stimulate discussion on how to improve education and training in this field. The results of a pilot survey conducted among the students enrolled for this programme are presented. Their responses reflect a positive attitude to the programme, especially concerning the interconnectedness of modules, the fostering of environmental awareness, and its usefulness for career objectives.
Sustainability takes time
Authors: Downey Peter R.
Published: April 2004

This is a story of transformation at Sheffield Hallam University, UK. It describes the progress and thinking along the path to introducing the university's vision of sustainability since the conclusion of EMSU 1999.It describes how sustainable practice has been incorporated within the formal democratic structures of the university, and describes the results of the initial environmental review and the early experiences and outcomes of target setting. The paper does not ignore those areas where there has not been success. It considers the involvement of the university in the UK Higher Education Programme for Sustainability (HEPS) directed by the Forum for the Future, and the advantages of engagement with the student community. The paper considers the early introduction of corporate social responsibility. It concludes with an aide memoir (currently in development) to assist all managers at the university in considering the impact of their planned actions on sustainability.
Environmental management at Swedish universities
Authors: Arvidsson Karin
Published: April 2004

Abstract Since1996, all Swedish public authorities, which includes most universities, have been made responsible for contributing to the sustainable development of the society. Swedish universities are thus required to submit annual environmental reports about their policies, structures and actions. This study provides a review of the activities that Swedish universities have undertaken so far. Reports from the year 2000 show that all 25 participating universities conducted the first environmental review. Most universities stopped there, although one – Mälardalen University – has gone all the way to ISO 14001 certification. The findings of the study suggest that universities, which have been participating for some years in the project, are further along the line than those that joined recently. There is also some indication that environmental‐management‐system (EMS) work is easier for the smaller universities, which can mobilise around a single goal.
The nature of the client‐personal business advisor relationship within Business Link
Authors: Lean Jonathan , Down Simon , Sadler‐Smith Eugene
Published: April 2004

The paper reports upon the findings of a national survey of Personal Business Advisors (PBAs). It examines the nature of the client‐PBA relationship in terms of how relationships are established with growth firms and how they are maintained over the long term. Results show that a range of different approaches are currently used to identify growth businesses. Other findings indicate that the current role of the PBA is a broad one, extending beyond the client focus originally envisaged by the DTI. It is argued that financial targets are an important influence upon the nature of the client‐PBA relationship.
Partnerships and networks: lessons from facilitating entrepreneurship
Authors: Maniukiewicz Carolyn , Williams Sarah , Keogh William
Published: April 2004

The delivery of assistance to SMEs, provided by enterprise councils at the local level, can vary between those bodies which are innovative and those which are pedestrian in their approach. Although it is generally accepted that most small firms in the UK sell to local markets, SMEs based within the Aberdeen area of Scotland play an important role in exporting and employment. The potential for birth and growth of firms exists in a number of targeted key sectors which aid the economic development of the Aberdeen area. However, assistance is required to bring people together in order to encourage networking, and this paper seeks to explore the process of facilitating an enterprise culture by examining the collaboration and partnership roles played by a LEC and a university in initiatives which foster enterprise. The relationship of the researchers and practitioners is similar to the model outlined by Oakey and Mukhtar where research and practice are used to inform each other, over time, to identify policy needs. The initiatives examined in this paper are the Entrepreneurs’ Club where established entrepreneurs mix with others at the new venture stage, and the Chrysalis Elite programme which links graduates with existing owner managers, creating a work‐based project involving groups of students. These links extend to the wider business community and organisations, including local entrepreneurs (who provide prizes and guidance), 3i and the Local Investors Network Company (LINC), who offer advice and opportunities. The main outcomes for policy in this paper are that collaboration between a LEC and a university can be very effective in assisting individuals or groups to meet the challenge of building entrepreneurial networks and that effective support can be provided for students to gain experience from the business community.