bluuebunny/crossref_metadata_2025 huggingface dataset:
Driving force and composition for multicomponent gas hydrate nucleation from supersaturated aqueous solutions
Authors: Anklam Mark R. , Firoozabadi Abbas
Published: November 2004

The expression for driving force is presented for multicomponent gas hydrate nucleation in an aqueous phase. The derivation includes working equations for predicting the composition of a hydrate nucleus. The results for driving force in multicomponent systems show a significant effect of the composition of the hydrate nucleus. All past work assume a fixed composition based on the three-phase equilibrium point independent of subcooling and supersaturation.
Dynamic light scattering study of the dynamics of a gelled polymeric micellar system
Authors: Castelletto V. , Hamley I. W. , Waigh T. A.
Published: November 2004

The dynamics of the E92B18/water system are studied by dynamic light scattering (DLS) in the liquid, soft gel, and hard gel phases. Both the liquid and the soft gel phases are micellar phases, although the structural order is higher in the soft gel phase than in the liquid phase. The hard gel phase corresponds to a face-centered cubic arrangement of micelles. DLS results show that the dilute liquid phase is characterized by a single characteristic time τ1 associated with the diffusion of the micelles. In addition, a second characteristic time τ̄2 associated with the presence of micellar clusters in the system is identified in the concentrated liquid and in the soft gel phases. According to these results, DLS suggests that the structure of the soft gel phase comprises micellar clusters coexisting with micellar fluid, in good agreement with hypotheses from our previous work. The dynamics of the system slows down as the hard gel phase is approached and a plateau is observed in the DLS correlation function. The structure of the hard gel is “softened” upon increasing temperature and/or decreasing concentration.
Nonadiabatic transitions in the exit channel of atom-molecule collisions: Fine-structure branching in Na+N2
Authors: Figl C. , Goldstein R. , Grosser J. , Hoffmann O. , Rebentrost F.
Published: November 2004

We study Na+N2 collisions by laser excitation of the collision complex in a differential scattering experiment. The measured relative population of the Na(3p) fine-structure levels reflects the nonadiabatic transitions occuring in the exit channel of the collision. Theoretical results obtained with a classical-path formalism and accurate quantum chemical data for NaN2 are found to be in good agreement. The presence of a conical intersection for the T-shaped geometry has a profound influence on the observed fine-structure branching.
Landau model of the direct isotropic to smectic-CA* phase transition in antiferroelectric liquid crystals
Authors: Mukherjee Prabir K. , Giesselmann Frank
Published: November 2004

An orientational order parameter is proposed for the isotropic to smectic CA* phase transition in antiferroelectric liquid crystals. A phenomenological theory is developed to describe the direct isotropic to smectic-CA* phase transition on the basis of a free energy expansion. The free energy is written in terms of the coupled order parameters including the antipolar correlations. We present a detailed analysis of the different phases that can occur and analyze the question: under which conditions a direct isotropic to smectic-CA* phase transition is possible when compared to other phase transitions? The theoretical results are compared with experimental results.
Cooperative effects, transport and entropy in simple liquids
Authors: Petravic Janka
Published: November 2004

We systematically investigate the cooperative effects in shear stress relaxation using equilibrium molecular-dynamics simulations in periodic boundary conditions containing a variable degree of strain. We show that, even in simple liquids, shear stress relaxation is a cooperative effect associated with a correlation length that increases with isobaric decrease in temperature. If the system size is less than the correlation length, shear stress in the system is determined by the boundary strain. Transport, however, does not depend on the boundary conditions. We relate these two effects to the number and properties of the configurations accessible to the system.
Nonanalytic curvature contributions to solvation free energies: Influence of drying
Authors: Evans R. , Henderson J. R. , Roth R.
Published: November 2004

We investigate the solvation of a hard spherical cavity, of radius R, immersed in a fluid for which the interparticle forces are short ranged. For thermodynamic states lying close to the liquid binodal, where the chemical potential deviation δμ≡μ−μco(T) is very small and positive, complete wetting by gas (drying) occurs and two regimes of interfacial behavior can be identified. These are characterized by the length scale Rc=2γgl∞/(Δρδμ), where γgl∞ is the planar gas–liquid surface tension and Δρ is the difference in coexisting densities at temperature T. For R>Rc, the interfacial free energy and the density profile of the fluid near the hard wall can be expanded in powers of the curvature R−1, in keeping with the analysis of Stillinger and Cotter [J. Chem. Phys. 55, 3449 (1971)]. In the other regime, R<Rc, the interfacial free energy and its derivatives acquire terms depending on ln R. Since Rc−1 can be made arbitrarily small this implies nonanalytic behavior, as R−1→0, of the work of formation of a hard spherical cavity and of the Gibbs adsorption and the fluid density at contact with the wall. Our analysis, which is based on an effective interfacial Hamiltonian combined with exact statistical mechanical sum rules, is confirmed fully by the results of microscopic density functional calculations for a square-well fluid. We discuss the repercussions of our results for solvation phenomena, emphasizing that nonanalytic behavior equivalent to that we find for complete drying in solvophobic systems will also arise in the case of complete wetting, i.e. when liquid films are adsorbed on the surface of large (colloidal) particles or at curved substrates. We reassess various results in the important but neglected Stillinger–Cotter paper, where drying was not considered explicitly, in the light of our present analysis.
Proton dynamics in the perchloric acid clathrate hydrate HClO4⋅5.5H2O
Authors: Desmedt Arnaud , Stallmach Frank , Lechner Ruep E. , Cavagnat Dominique , Lassègues Jean-Claude , Guillaume François , Grondin Joseph , Gonzalez Miguel A.
Published: November 2004

In the perchloric acid clathrate hydrate HClO4⋅5.5H2O, the perchlorate anions are contained inside an aqueous host crystalline matrix, positively charged because of the presence of delocalized acidic protons. Our experimental results demonstrate that the microscopic mechanisms of proton conductivity in this system are effective on a time scale ranging from nanosecond to picosecond. In the present paper, we discuss more specifically on the relaxation processes occurring on a nanosecond time scale by combining high-resolution quasielastic neutron scattering and H1 pulse-field-gradient nuclear magnetic resonance experiments. The combination of these two techniques allows us to probe proton dynamics in both space and time domains. The existence of two types of proton dynamical processes has been identified. The slowest one is associated to long-range translational diffusion of protons between crystallographic oxygen sites and has been precisely characterized with a self-diffusion coefficient of 3.5×10−8 cm2/s at 220 K and an activation energy of 29.2±1.4 kJ/mol. The fastest dynamical process is due to water molecules’ reorientations occurring every 0.7 ns at 220 K with an activation energy of 17.4±1.5 kJ/mol. This powerful multitechnique approach provides important information required to understand the microscopic origin of proton transport in an ionic clathrate hydrate.
Conformation selective assembly of carboxyphenyl substituted porphyrins on Au (111)
Authors: Yokoyama Takashi , Kamikado Toshiya , Yokoyama Shiyoshi , Mashiko Shinro
Published: November 2004

The selective assembly of carboxyphenyl substituted porphyrins on the Au (111) surface has been studied using scanning tunneling microscopy. We find that conformational isomers of the porphyrins are induced upon adsorption and are selectively assembled into hydrogen-bonded supramolecular clusters or wires on the surface. The conformation selective assembly is attributed to the coplanar intermolecular interactions between hydrogen-bonded carboxyphenyl groups.
The role of plastic β-hairpin and weak hydrophobic core in the stability and unfolding of a full sequence design protein
Authors: Lei Hongxing , Duan Yong
Published: November 2004

In this study, the thermal stability of a designed α/β protein FSD (full sequence design) was studied by explicit solvent simulations at three moderate temperatures, 273 K, 300 K, and 330 K. The average properties of the ten trajectories at each temperature were analyzed. The thermal unfolding, as judged by backbone root-mean-square deviation and percentage of native contacts, was displayed with increased sampling outside of the native basin as the temperature was raised. The positional fluctuation of the hairpin residues was significantly higher than that of the helix residues at all three temperatures. The hairpin segment displayed certain plasticity even at 273 K. Apart from the terminal residues, the highest fluctuation was shown in the turn residues 7–9. Secondary structure analysis manifested the structural heterogeneity of the hairpin segment. It was also revealed by the simulation that the hydrophobic core was vulnerable to thermal denaturation. Consistent with the experiment, the I7Y mutation in the double mutant FSD-EY (FSD with mutations Q1E and I7Y) dramatically increased the protein stability in the simulation, suggesting that the plasticity of the hairpin can be partially compensated by a stronger hydrophobic core. As for the unfolding pathway, the breathing of the hydrophobic core and the separation of the two secondary structure elements (α helix and β hairpin) was the initiation step of the unfolding. The loss of global contacts from the separation further destabilized the hairpin structure and also led to the unwinding of the helix.
Electrosprays of very polar liquids at low flow rates
Authors: Higuera F. J. , Barrero A.
Published: November 2004

An order-of-magnitude analysis of the flow around the tip of the meniscus and in the jet of an electrospray of a very polar liquid in the cone-jet mode is reported. Assuming that a long stationary jet exists, the relationship between the electric current and the flow rate is predicted to change from the well-known square root law for high flow rates to a linear law in a regime of low but experimentally realizable flow rates in which the electric field of the liquid polarizes the surface. The current is independent of the viscosity of the liquid in both flow rate regimes.
Radial mixing of granular materials in a rotating cylinder: Experimental determination of particle self-diffusivity
Authors: Hajra Suman K. , Khakhar D. V.
Published: November 2004

Particle self-diffusion has a significant effect on mixing and thus on performance of rotating cylinder systems such as rotary kilns and drum mixers. We study experimentally the radial mixing of monodisperse beads of different colors in a quasi-two-dimensional cylinder rotated in the continuous flow regime. In this regime a shallow surface layer of particles flows steadily while the rest of the material rotates as a solid body. The initial distribution of tracer particles is taken to be radially symmetric and cylinder is taken to be half full. Both facilitate estimation of the particle self-diffusivity since the evolving concentration distribution during mixing in this case is radial for most part and the mixing in these conditions is shown to be dominated by diffusion of particles. A qualitative study of the mixing is carried out using digital photography. Radial number fraction profiles of the tracer particles are obtained by bulk sampling. Since mixing occurs only in the flowing layer, mixing is considered in terms of “passes” defined as the number of times the material in the bed entirely flows through the layer. Experimental results indicate that the mixing per pass decreases with increasing rotational speed, increases with increasing particle size, and is nearly independent of cylinder size. The mixed state captured by digital photography and the measured radial concentration profiles are well described by a convective diffusion model, using diffusivity as a fitting parameter. The diffusivity obtained from the model follows the scaling proposed by Savage [“Disorder, diffusion, and structure formation in granular flow,” Disorder and Granular Media, edited by A. Hansen and D. Bideau (Elsevier, Amsterdam, 1993), pp. 255–285] and a simple expression for the diffusivity is obtained in terms of the particle diameter and the static and dynamic angles of repose.
Atomistic simulations of biologically realistic transmembrane potential gradients
Authors: Sachs Jonathan N. , Crozier Paul S. , Woolf Thomas B.
Published: November 2004

We present all-atom molecular dynamics simulations of biologically realistic transmembrane potential gradients across a DMPC bilayer. These simulations are the first to model this gradient in all-atom detail, with the field generated solely by explicit ion dynamics. Unlike traditional bilayer simulations that have one bilayer per unit cell, we simulate a 170 mV potential gradient by using a unit cell consisting of three salt-water baths separated by two bilayers, with full three-dimensional periodicity. The study shows that current computational resources are powerful enough to generate a truly electrified interface, as we show the predicted effect of the field on the overall charge distribution. Additionally, starting from Poisson’s equation, we show a new derivation of the double integral equation for calculating the potential profile in systems with this type of periodicity.
Real-time detection of doorway states in the intramolecular vibrational energy redistribution of the OH/OD stretch vibration of phenol
Authors: Yamada Yuji , Mikami Naohiko , Ebata Takayuki
Published: November 2004

A picosecond time-resolved IR-UV pump–probe spectroscopic study was carried out for the intramolecular vibrational energy redistribution of the OH/OD stretching vibration of isolated phenol and its isotopomers in supersonic beams. The time evolution due to IVR showed a significant isotope effect; the OH stretch vibration showed a single exponential decay and its lifetime is greatly lengthened upon the deuterium substitution of the CH group. The OD stretch vibration exhibited prominent quantum beats. Especially, in phenol-d1 (C6H5OD), the electronic transitions from the doorway states were clearly observed. They exhibited an out-of-phase quantum beat with respect to that of the OD stretch level and disappeared due to further IVR to the dense bath states. The transient spectra as well as the time evolution clearly evidenced the tier-model of the description of intramolecular vibrational energy redistribution.
Rydberg–London potential for diatomic molecules and unbonded atom pairs
Authors: Cahill Kevin , Parsegian V. Adrian
Published: November 2004

We propose and test a pair potential that is accurate at all relevant distances and simple enough for use in large-scale computer simulations. A combination of the Rydberg potential from spectroscopy and the London inverse-sixth-power energy, the proposed form fits spectroscopically determined potentials better than the Morse, Varnshi, and Hulburt–Hirschfelder potentials and much better than the Lennard-Jones and harmonic potentials. At long distances, it goes smoothly to the London force appropriate for gases and preserves van der Waals’s “continuity of the gas and liquid states,” which is routinely violated by coefficients assigned to the Lennard-Jones 6-12 form.
Genetic analysis of quantitative traits in rice (Oryza sativa L.) exposed to salinity
Authors: Mahmood T. , Turner M. , Stoddard F. L. , Javed M. A.
Published: November 2004

Abstract The release of rice cultivars with improved performance in saline environments is reliant on an understanding of the genetic control of plant and panicle characters in plants exposed to salinity. The regulation of agro-physiological characters of rice plants grown in a saline environment was thus investigated. A complete diallel cross was prepared from 8 parental rice accessions with a range of tolerances to salinity. F1 hybrids and parents were grown in saline-sodic soil in artificially constructed salinity blocks. At maturity, the plant height, productive tiller number per plant, panicle length, primary branch number per panicle, panicle fertility, time to maturity, shoot dry weight, shoot Na, Ca, and K concentrations, and paddy yield were recorded. Additive and dominant genetic effects contributed significantly to the total heritable variation observed for plant height, panicle length, and sodium and potassium shoot concentrations. Additive genetic effects were important for the expression of variation of productive tiller number per plant and the number of primary branches per panicle, while dominant genetic effects were important for the expression of variation of the number of days to maturity. Plant height and primary branch number per panicle are traits that may be readily improved by selection in saline environments.
Nitrogen utilisation and rumen function in Menz rams supplemented with foliages of Lablab purpureus or graded levels of Leucaena pallida 14203 and Sesbania sesban 1198
Authors: Melaku Solomon
Published: November 2004

Thirty-five male Menz rams (19.3 ± 0.87 kg, mean ± s.d.) fed on a basal diet of tef (Eragrostis tef) straw were used in a randomised block design to study the effects of supplementing with one level of Lablab purpureus (lablab), at 1.2% LW (230 g DM/day), and 3 graded levels of Leucaena pallida 14203 or Sesbania sesban 1198 at 0.9% LW (170 g DM/day), 1.2% LW (230 g DM/day), and 1.5% LW (290 g DM/day) on nitrogen (N) intake, microbial N yield, N retention, levels of rumen pH, and ammonia N. Five rams were used in each of the 7 treatments. The rams were adapted to treatment feeds for 3 weeks, followed by the collection of faeces and urine for 7 days by keeping them in metabolic cages. Graded levels of L. pallida resulted in lower (P < 0.001) daily microbial N yield and lower (P < 0.001) efficiency of microbial N yield per kg organic matter digested in the rumen and per MJ metabolisable energy than graded levels of S. sesban. Urinary N excretion was higher (P < 0.001) in S. sesban and Lablab supplemented animals than those supplemented with L. pallida, and the opposite was true for faecal and total N excretion. However, these did not result in treatment differences in N retention. L. pallida promoted lower (P < 0.001) mean rumen NH3-N level and higher mean rumen pH than the other supplement feeds. It is concluded that the lowest level of either L. pallida or S. sesban supplementation was adequate to promote comparable N retention to the 2 higher levels of supplementation.
Genetic variation in water-soluble carbohydrate concentration in diverse cultivars of Dactylis glomerata L. during vegetative growth
Authors: Sanada Y. , Takai T. , Yamada T.
Published: November 2004

The water-soluble carbohydrate (WSC) content of Dactylis glomerata L. (cocksfoot) during vegetative growth is lower than that of other temperate grasses. Variation in the WSC content of vegetative growth among cultivars was measured in order to assess the potential to improve forage quality. There were significant differences among cultivars for WSC content (P < 0.01) in all maturity groups. Average WSC content of the late (L) maturity group was higher than that of the early (E) and medium (M) maturity groups. Variation in the WSC content was largest among group L cultivars and smallest in group M. The WSC content of cultivars in groups M and L was consistent across 2 years (interactions between cultivars and years were not significant). Brown stripe infection was shown to reduce WSC content in susceptible cultivars. As a result of multiple regression analysis with WSC content as the dependent variable, dry matter content, heading date, thickness of stems, and resistance to brown stripe were selected as independent variables that were correlated with WSC. Therefore, variation for these traits must also be monitored in any program to increase WSC content in orchardgrass.
Targeted disruption of luteinizing hormone β-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility
Authors: Ma Xiaoping , Dong Yanlan , Matzuk Martin M. , Kumar T. Rajendra
Published: November 2004

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) act on gonadal cells to promote steroidogenesis and gametogenesis. Clarifying the
in vivo
roles of LH and FSH permits a feasible approach to contraception involving selective blockade of gonadotropin action. One way to address these physiologically important problems is to generate mice with an isolated LH deficiency and compare them with existing FSH loss-of-function mice. To model human reproductive disorders involving loss of LH function and to define LH-responsive genes, we produced knockout mice lacking the hormone-specific LHβ-subunit. LHβ-null mice are viable but demonstrate postnatal defects in gonadal growth and function resulting in infertility. Mutant males have decreased testes size, prominent Leydig cell hypoplasia, defects in expression of genes encoding steroid biosynthesis pathway enzymes, and reduced testosterone levels. Furthermore, spermatogenesis is blocked at the round spermatid stage, causing a total absence of the elongated spermatids. Mutant female mice are hypogonadal and demonstrate decreased levels of serum estradiol and progesterone. Ovarian histology demonstrates normal thecal layer, defects in folliculogenesis including many degenerating antral follicles, and absence of corpora lutea. The defects in both sexes are not secondary to aberrant FSH regulation, because FSH levels were unaffected in null mice. Finally, both male and female null mice can be pharmacologically rescued by exogenous human chorionic gonadotropin, indicating that LH-responsiveness of the target cells is not irreversibly lost. Thus, LHβ null mice represent a model to study the consequences of an isolated deficiency of LH ligand in reproduction, while retaining normal LH-responsiveness in target cells.
Agrobacterium
VirB10, an ATP energy sensor required for type IV secretion
Authors: Cascales Eric , Christie Peter J.
Published: November 2004

Bacteria use type IV secretion systems (T4SS) to translocate DNA and protein substrates to target cells of phylogenetically diverse taxa. Recently, by use of an assay termed transfer DNA immunoprecipitation (TrIP), we described the translocation route for a DNA substrate [T-DNA, portion of the Ti (tumor-inducing) plasmid that is transferred to plant cells] of the
Agrobacterium tumefaciens
VirB/D4 T4SS in terms of a series of temporally and spatially ordered substrate contacts with subunits of the secretion channel. Here, we report that the bitopic inner membrane protein VirB10 undergoes a structural transition in response to ATP utilization by the VirD4 and VirB11 ATP-binding subunits, as monitored by protease susceptibility. VirB10 interacts with inner membrane VirD4 independently of cellular energetic status, whereas the energy-induced conformational change is required for VirB10 complex formation with an outer membrane-associated heterodimer of VirB7 lipoprotein and VirB9, as shown by coimmunoprecipitation. Under these conditions, the T-DNA substrate is delivered from the inner membrane channel components VirB6 and VirB8 to periplasmic and outer membrane-associated VirB2 pilin and VirB9. We propose that VirD4 and VirB11 coordinate the ATP-dependent formation of a VirB10 “bridge” between inner and outer membrane subassemblies of the VirB/D4 T4SS, and that this morphogenetic event is required for T-DNA translocation across the
A. tumefaciens
cell envelope.
Phenotypic differences between
Salmonella
and
Escherichia coli
resulting from the disparate regulation of homologous genes
Authors: Winfield Mollie D. , Groisman Eduardo A.
Published: November 2004

Phenotypic differences among closely related bacteria have been largely ascribed to species-specific genes, such as those residing in pathogenicity islands. However, we now report that the differential regulation of homologous genes is the mechanism responsible for the divergence of the enteric bacteria
Salmonella enterica
and
Escherichia coli
in their ability to make LPS modifications mediating resistance to the antibiotic polymyxin B. In
S. enterica
serovar Typhimurium, the PmrA/PmrB two-component system governing polymyxin B resistance is induced in low Mg
2+
in a process that requires the PmrD protein and by Fe
3+
in a PmrD-independent fashion. We establish that
E. coli
K-12 induces PmrA-activated gene transcription and polymyxin B resistance in response to Fe
3+
, but that it is blind to the low Mg
2+
signal. The highly divergent PmrD protein is responsible for this phenotype as replacement of the
E. coli pmrD
gene by its
Salmonella
counterpart resulted in an
E. coli
strain that transcribed PmrA-activated genes and displayed polymyxin B resistance under the same conditions as
Salmonella
. Molecular analysis of natural isolates of
E. coli
and
Salmonella
revealed that the PmrD proteins are conserved within each genus and that selection might have driven the divergence between the
Salmonella
and
E. coli
PmrD proteins. Investigation of PmrD function demonstrated statistically different distributions for the
Salmonella
and
E. coli
isolates in PmrD-dependent transcription occurring in low Mg
2+
. Our results suggest that the differential regulation of conserved genes may have ecological consequences, determining the range of niches a microorganism can occupy.
Restricted inactivation of serum response factor to the cardiovascular system
Authors: Miano Joseph M. , Ramanan Narendrakumar , Georger Mary A. , de Mesy Bentley Karen L. , Emerson Rachael L. , Balza Robert O. , Xiao Qi , Weiler Hartmut , Ginty David D. , Misra Ravi P.
Published: November 2004

Serum response factor (SRF) directs programs of gene expression linked to growth and muscle differentiation. To investigate the role of SRF in cardiovascular development, we generated mice in which SRF is knocked out in >80% of cardiomyocytes and >50% of vascular smooth muscle cells (SMC) through SM22α-Cre-mediated excision of SRF's promoter and first exon. Mutant mice display vascular patterning, cardiac looping, and SRF-dependent gene expression through embryonic day (e)9.5. At e10.5, attenuation in cardiac trabeculation and compact layer expansion is noted, with an attendant decrease in vascular SMC recruitment to the dorsal aorta. Ultrastructurally, cardiac sarcomeres and Z disks are highly disorganized in mutant embryos. Moreover, SRF mutant mice exhibit vascular SMC lacking organizing actin/intermediate filament bundles. These structural defects in the heart and vasculature coincide with decreases in SRF-dependent gene expression, such that by e11.5, when mutant embryos succumb to death, no SRF-dependent mRNA expression is evident. These results suggest a vital role for SRF in contractile/cytoskeletal architecture necessary for the proper assembly and function of cardiomyocytes and vascular SMC.
Structural basis of activity and allosteric control of diguanylate cyclase
Authors: Chan Carmen , Paul Ralf , Samoray Dietrich , Amiot Nicolas C. , Giese Bernd , Jenal Urs , Schirmer Tilman
Published: November 2004

Recent discoveries suggest that a novel second messenger, bis-(3′→5′)-cyclic di-GMP (c-diGMP), is extensively used by bacteria to control multicellular behavior. Condensation of two GTP to the dinucleotide is catalyzed by the widely distributed diguanylate cyclase (DGC or GGDEF) domain that occurs in various combinations with sensory and/or regulatory modules. The crystal structure of the unorthodox response regulator PleD from
Caulobacter crescentus
, which consists of two CheY-like receiver domains and a DGC domain, has been solved in complex with the product c-diGMP. PleD forms a dimer with the CheY-like domains (the stem) mediating weak monomer–monomer interactions. The fold of the DGC domain is similar to adenylate cyclase, but the nucleotide-binding mode is substantially different. The guanine base is H-bonded to Asn-335 and Asp-344, whereas the ribosyl and α-phosphate moieties extend over the β2-β3-hairpin that carries the GGEEF signature motif. In the crystal, c-diGMP molecules are crosslinking active sites of adjacent dimers. It is inferred that, in solution, the two DGC domains of a dimer align in a two-fold symmetric way to catalyze c-diGMP synthesis. Two mutually intercalated c-diGMP molecules are found tightly bound at the stem–DGC interface. This allosteric site explains the observed noncompetitive product inhibition. We propose that product inhibition is due to domain immobilization and sets an upper limit for the concentration of this second messenger in the cell.
Neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral RNA interference
Authors: Thakker Deepak R. , Natt Francois , Hüsken Dieter , Maier Rainer , Müller Matthias , van der Putten Herman , Hoyer Daniel , Cryan John F.
Published: November 2004

Gene expression analysis implicates an increasing number of novel genes in the brain as potential targets for the treatment of neurological and psychiatric disorders. Frequently, these genes are ubiquitously expressed in the brain and, thus, may contribute to a pathophysiological state through actions in several brain nuclei. Current strategies employing genetically modified animals for
in vivo
validation of such targets are time-consuming and often limited by developmental adaptations. Somatic gene manipulation using viral-mediated RNA interference (RNAi) has emerged recently, although restricting the target validation to specific brain nuclei. We investigated whether nonviral infusion of short interfering RNA (siRNA) into the ventricular system would enable a sequence-specific gene knockdown. The temporality and extent of siRNA-induced down-regulation were analyzed by targeting a transgene, EGFP, in mice overexpressing EGFP. Extensive knockdown of EGFP was observed, especially in regions adjacent or dorsoventrally and mediolaterally distant to the infusion site (dorsal third ventricle), with lesser knockdown in more distal regions. We challenged our RNAi approach to generate a specific knockdown of an endogenous gene, encoding the dopamine transporter (DAT) in regions (ventral midbrain) far distal to the infusion site. DAT-siRNA infusion in adult mice produced a significant down-regulation of DAT mRNA and protein in the brain and also elicited a temporal hyperlocomotor response similar to that (but delayed) obtained upon infusion of GBR-12909, a pharmacologically selective DAT inhibitor. Application of this nonviral RNAi approach may accelerate target validation for neuropsychiatric disorders that involve a complex interplay of gene(s) from various brain regions.
Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development
Authors: Yan Ming , Burel Sebastien A. , Peterson Luke F. , Kanbe Eiki , Iwasaki Hiromi , Boyapati Anita , Hines Robert , Akashi Koichi , Zhang Dong-Er
Published: November 2004

Normal blood-cell differentiation is controlled by regulated gene expression and signal transduction. Transcription deregulation due to chromosomal translocation is a common theme in hematopoietic neoplasms. AML1-ETO, which is a fusion protein generated by the 8;21 translocation that is commonly associated with the development of acute myeloid leukemia, fuses the AML1 runx family DNA-binding transcription factor to the ETO corepressor that associates with histone deacetylase complexes. Analyses have demonstrated that AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. Here, we report that the loss of the molecular events of AML1-ETO C-terminal NCoR/SMRT-interacting domain transforms AML1-ETO into a potent leukemogenic protein. Contrary to full-length AML1-ETO, the truncated form promotes
in vitro
growth and does not obstruct the cell-cycle machinery. These observations suggest a previously uncharacterized mechanism of tumorigenesis, in which secondary mutation(s) in molecular events disrupting the function of a domain of the oncogene promote the development of malignancy.
Use of coherent control methods through scattering biological tissue to achieve functional imaging
Authors: Dela Cruz Johanna M. , Pastirk Igor , Comstock Matthew , Lozovoy Vadim V. , Dantus Marcos
Published: November 2004

We test whether coherent control methods based on ultrashort-pulse phase shaping can be applied when the laser light propagates through biological tissue. Our results demonstrate experimentally that the spectral-phase properties of shaped laser pulses optimized to achieve selective two-photon excitation survive as the laser pulses propagate through tissue. This observation is used to obtain functional images based on selective two-photon excitation of a pH-sensitive chromophore in a sample that is placed behind a slice of biological tissue. Our observation of coherent control through scattering tissue suggests possibilities in multiphoton-based imaging and photodynamic therapy.
Single-cell FRET imaging of phosphatase activity in the
Escherichia coli
chemotaxis system
Authors: Vaknin Ady , Berg Howard C.
Published: November 2004

Two-component signaling systems, in which a receptor-coupled kinase is used to control the phosphorylation level of a response regulator, are commonly used in bacteria to sense their environment. In the chemotaxis system of
Escherichia coli
, the receptors, and thus the kinase, are clustered on the inner cell membrane. The phosphatase of this system also is recruited to receptor clusters, but the reason for this association is not clear. By using FRET imaging of single cells, we show that
in vivo
the phosphatase activity is substantially larger at the cluster, indicating that the signaling
source
(the kinase) and the signaling
sink
(the phosphatase) tend to be located at the same place in the cell. When this association is disrupted, a gradient in the concentration of the phosphorylated response regulator appears, and the chemotactic response is degraded. Such colocalization is inevitable in systems in which the activity of the kinase and the phosphatase are produced by the same enzyme. Evidently, this design enables a more rapid and spatially uniform response.
Universities and government‐sponsored contract research: an Australian case study
Authors: HARMAN GRANT , OLLIF CATHRYN
Published: November 2004

Based on interviews, this article provides a case study of the experiences of academic staff at one Australian regional university in undertaking contract research projects sponsored by government departments and agencies. Academics from a surprisingly diverse range of disciplines are attracted to government‐sponsored research for a variety of reasons but particularly important is the financial support provided for research projects and postgraduate research students. Projects vary in scale, amounts of funding involved and purposes, with research activities covering a wide range of different activities including collection and analysis of data, provision of documentation on good practice, design of implementation strategies, evaluations, organisational reviews and policy recommendations. Overall, respondents are highly positive about their experiences, despite problems such as delays in payment of funds, inappropriately restricted timelines, frequent changes in senior agency personnel, unrealistic expectations, and restrictions in the use of data and publication of results. While many academics from different disciplines provide policy recommendations and carry out evaluative studies, few are well informed about the extent to which their work is actually utilised.
Innovation–export linkages within different cluster models: a case study from the Australian wine industry
Authors: AYLWARD DAVID
Published: November 2004

This paper examines innovation and export linkages within different levels of cluster development. The aim of the paper, using empirical data from the Australian wine industry, is to demonstrate that the association between innovation and export activity intensifies as the cluster develops. Dividing wine clusters into ‘innovative’ (highly developed) and ‘organised’ (less developed) models, the paper uses selected core indicators of innovation and export activity to explore levels of integration within each model. This integration is examined in the context of Porter’s theory of ‘competitive advantage’, showing how these lessons can be translated to industry clusters in general.
Injecting and non‐injecting cocaine use in Sydney, Australia: physical and psychological morbidity
Authors: KAYE SHARLENE , DARKE SHANE
Published: November 2004

This study aimed to examine the physical and psychological harms of cocaine use and investigate the role of injecting versus non‐injecting routes of administration in the severity of such harms. Two hundred and twelve cocaine users from inner‐city and southwestern Sydney were administered a structured interview containing sections on demographics, drug treatment history, drug use history, cocaine use patterns, cocaine dependence and physical and psychological problems associated with cocaine use. Serious physical and psychological symptoms were prevalent among both injecting and non‐injecting cocaine users. The prevalence and extent of symptoms was greater among injecting cocaine users, however route of administration did not prove to be a significant independent predictor of harm when other factors, such as frequency of use and level of dependence, were taken into account. While the level of physical and psychological harm was greater among cocaine injectors, it would appear that factors engendered by injecting, such as more frequent use and higher levels of dependence, result in higher levels of harm, rather than the route of administration per se. Physical and psychological problems were also reported among infrequent users, suggesting that cocaine can cause harm irrespective of frequency or method of use. Harm reduction initiatives should be targeted towards all cocaine users, not just those who seek treatment for dependence or present with acute medical complications.
Alfred Marshall's Idea of Progress and Sustainable Development
Authors: Caldari Katia
Published: November 2004

For a long time, Marshall's chief contribution to economic science was considered to be Book V ofPrinciples of Economics, which is the “analytic core” of his thought. Book V, “General Relations of Demand, Supply and Value,” deals with the important theme of economic equilibrium thatipso factorules out any possibility of coping with economic development. When Alfred Marshall describes Book V, he points out that “it is not descriptive, nor does it deal constructively with real problems. But it sets out the theoreticalbackboneof our knowledge of the causes that govern value” (1961, vol. 1, p. 324); in short, it “deals with abstractions” (1898, p. 52). The existence of Book V has been supposed by some scholars to be sound enough proof that Alfred Marshall was not interested in the question of economic development. More recently, however, it has been suggested that one of the main Marshallian concerns was economic development,—“the high theme of economic progress,” as he called it (Marshall 1961, vol. 1, p. 461).
Characteristics of Tobacco‐Smoking Problem Gamblers Calling a Gambling Helpline
Authors: Potenza Marc N. , Steinberg Marvin A. , McLaughlin Susan D. , Wu Ran , Rounsaville Bruce J. , Krishnan‐Sarin Suchitra , George Tony P. , O'Malley Stephanie S.
Published: November 2004

Few studies have examined the smoking behaviors of problem gamblers. A high proportion of problem gamblers calling a gambling helpline reported daily tobacco smoking (43.1%). Problem gamblers reporting daily tobacco smoking more frequently acknowledged depression and suicidality secondary to gambling, gambling‐related arrests, alcohol and drug use problems, mental health treatment, and problems with casino slot machine gambling. The findings substantiate the relationship in problem gamblers between tobacco smoking and psychiatric symptomatology, particularly other substance use problems. The high proportion of callers reporting daily tobacco smoking highlights the need for enhanced smoking cessation efforts in problem gamblers.
Usage of Antifungal Drugs for Therapy of Genital CandidaInfections, Purchased as Over‐the‐Counter Products or by Prescription: 2. Factors that May have Influenced the Marked Changes in Sales Volumes During the 1990s
Authors: Mårdh Per-Anders , Wågström Jolanta , Landgren Maria , Holmén Jan
Published: November 2004

Background: The epidemiology of vulvovaginal candidiasis (VVC) and such recurrent infections (RVVC) has been difficult to study as the majority of episodes of these conditions are self‐treated by the women affected. In
Sweden, all pharmacies are owned by the state and all prescriptions and over‐the‐counter (OTC) products, such as antifungals, are registered in a database, which offers unique possibilities to study the epidemiology of VVC/RVVC.

Objectives: To analyze all prescriptions and OTC products purchased for therapy of VVC/RVVC and to establish reasons for any observed variation in the sales figures.

Methods: Sales figures in the Swedish county of Skåne of antifungal drugs for therapy of VVC/RVVC were analyzed by the aid of the ‘ACS’ database of the National Corporation of Swedish Pharmacies for the years 1990–1999. The size of the female population in the county is approximately half a million.

Results: The study showed that 93% of all antifungal drugs for VVC/RVVC were sold as OTC products. An increase in sales of the drugs occurred until mid‐1993/94, followed by a decrease until end of the study period in 1999. Demographic factors (e.g. the number of female inhabitants in the county, pharmacies and health‐care
units), the pregnancy rate and pharmacy‐dependent factors (such as the introduction of shelves for selfselection of antifungal products) did not explain the observed variations in sales. Distinct short‐term variations in the number of prescriptions of fluconazole and itraconazole could be explained by drugs company sales campaigns and logistics factors in drug distribution. The sales volumes in the 33 municipalities in the county correlated with the density of the population, which was not the case for the total number of prescriptions
made in the county during the 1990s. The variation in antifungal drug sales was similar to that of hormonal intrauterine devices, but this was not the case for oral contraceptives. The total Swedish usage of antibiotics showed a similar variation to that of the antifungal drugs analyzed.

Conclusion: The study stresses the limited impact on the treatment of VVC/RVVC by the medical community. Behavior‐related factors in the female population are the most likely explanation for the marked variations found in the usage of drugs for the two conditions.
Human Parvovirus B19 VP2 Empty Capsids Bind to Human Villous Trophoblast Cells in vitro Via the Globoside Receptor
Authors: Wegner Carole C. , Jordan Jeanne A.
Published: November 2004

Background: Pregnant women acutely infected with human parvovirus B19 (B19) may transmit the virus to the developing fetus. The mechanism whereby the virus interacts with the placenta is unknown. It is known that
globoside receptor is required for successful infection of the target cells, which are the highly undifferentiated, actively dividing colony and burst‐form units of the erythroid series. Globoside is present on trophoblast cells which have intimate contact with maternal blood, and may therefore serve as a potential route for B19 transmission into the fetal compartment.

Objectives: The purpose of this study was to determine whether B19 VP2 capsids could bind to villous trophoblast cells in vitro and whether globoside was involved.

Methods: Binding of B19 VP2 empty capsid to first‐trimester villous trophoblast cells was assessed by multiple approaches, including ICC using either biotinylated B19 VP2 empty capsid or unlabeled B19 VP2 empty capsid. Quantification of viral binding involved I125
‐labeled B19 VP2 empty capsid. Competition studies included excess unlabeled empty capsids or pretreatment with globoside‐specific IgM antibody.

Results: Linear binding of B19 VP2 capsid to purified villous trophoblast cells in vitro was clearly demonstrated
(R2 = 0.9524). Competition studies revealed specificity of I125
‐labeled B19 VP2 capsid binding to villous trophoblast cells when pretreatment with either 60‐fold excess unlabeled B19 capsid or globoside‐specific IgM antibody took place. The results illustrated B19′s ability to bind in a specific manner to globoside‐containing
villous trophoblast cells.

Conclusion: We speculate that the globoside present on trophoblast cells may play a role in viral binding in vivo, which may facilitate B19 transmission across the maternal–fetal interface.
Verbal deficits in Down's syndrome and specific language impairment: a comparison
Authors: Laws Glynis , Bishop Dorothy V. M.
Published: November 2004

Background: Down's syndrome is a chromosome disorder characterized by a range of physical and psychological conditions, including language impairment. The severity of impairment is variable, and some components of the language system appear to be more affected than others. This description could also be applied to typically developing children diagnosed with specific language impairment.

Aims: To compare findings from the largely separate research literatures on these conditions, and to address the questions about whether the language pathology associated with Down's syndrome could be the same as that described as specific language impairment in typical development, and whether the two conditions could have similar causes.

Main Contribution: Research studies suggest similar patterns of language impairment in the two populations, and some similarities in underlying processing deficits.

Conclusions: Future research should consider whether similarities in the language behaviours associated with Down's syndrome and specific language impairment could be related to similarities at other levels of analysis, including neurological development and genetics.
Reflections on speech—language therapists' talk: implications for clinical practice and education
Authors: Ferguson Alison , Armstrong Elizabeth
Published: November 2004

Background: Research into the practices of speech–language therapists in clinical sessions is beginning to identify the way communication in clinical interactions both facilitates and potentially impedes the achievement of therapy goals.

Aims: This target article aims to raise the issues that arise from critical reflections on the communication of speech–language therapists for both clinical practice and clinical education of future speech–language therapists.

Methods & Procedures: The paper reviews the past and current literature into the communication of speech–language therapists with their clients and provide examples drawn from the authors' own empirical research.

Outcomes & Results: It is argued that one cannot assume that the current rhetoric regarding collaborative practice matches what is currently done in clinical work.

Conclusions: This paper calls attention to the need to evaluate critically the processes and nature of acculturation that occurs during the first stages of professional development as a student speech–language therapist through to the ongoing development of professional practice.