bluuebunny/crossref_metadata_2025 huggingface dataset:
Time for a re-think: Problems with the parallel distributed approach to semantic cognition
Authors: Quinlan Philip
Published: December 2008

Rogers & McClelland (R&M) have provided an impressive outline of the capabilities of a class of multi-layered perceptrons that mimic many aspects of human knowledge acquisition. Despite this success, in the literature several basic issues are raised and concerns are expressed. Indeed, the problems are so acute that a different way of thinking is called for. In this commentary it is suggested that rational models approach provides a promising alternative.
Semantic redintegration: Ecological invariance
Authors: Robbins Stephen E.
Published: December 2008

In proposing that their model can operate in the concrete, perceptual world, Rogers & McClelland (R&M) have not done justice to the complexities of the ecological sphere and its invariance laws. The structure of concrete events forces a different framework, both for retrieval of events and concepts defined across events, than that upon which the proposed model, rooted in essence in the verbal learning tradition, implicitly rests.
Reading Semantic Cognition as a theory of concepts
Authors: Snedeker Jesse
Published: December 2008

Any theory of semantic cognition is also a theory of concepts. There are two ways to construe the models presented by Rogers & McClelland (R&M) in Semantic Cognition. If we construe the input and output representations as concepts, then the models capture knowledge acquisition within a stable set of concepts. If we construe the hidden-layer representations as concepts, the models provide a simulation of conceptual change.
Agency, argument structure, and causal inference
Authors: ter Meulen Alice G. B.
Published: December 2008

Logically, weighting is transitive, but similarity is not, so clustering cannot be either. Entailments must help a child to review attribute lists more efficiently. Children's understanding of exceptions to generic claims precedes their ability to articulate explanations. So agency, as enabling constraint, may show coherent covariation with attributes, as mere extensional, observable effect of intensional entailments.
Distribution of axial lava domes along a superfast overlapping spreading center, 27–32°S on the East Pacific Rise
Authors: Bohnenstiehl D. R. , Howell J. K. , Hey R. N.
Published: December 2008

Deep‐towed DSL‐120 bathymetric data are used to investigate the pattern of lava dome formation along a superfast spreading portion of the southern East Pacific Rise (EPR), including the overlapping limbs of a giant (120 × 120 km) propagator near 29°S. Along the 670 km of the axis surveyed, 1172 small domes were identified using a closed contour algorithm. Their abundance, defined by spatial density, is well correlated with the along‐axis relief of the ridge crest. Where the western and eastern limbs plunge toward the overlap zone, densities are high (3–6 km−2); however, where the axial depth profile is shallow and flat, densities are comparably low (0.4 km−2). Volcanic domes within the low abundance areas are characterized by lower ratios of height to basal radius (0.15 versus 0.22), smaller maximum heights (18 versus 40 m), and a larger relative percentage of small versus large mounds. The zone of high dome abundance encompasses the overlapping limbs of the rift and extends more than 100 km to the north and south beyond the overlap zone. Domes form dominantly during low effusion rate, point‐source eruptions, which suggests that discontinuous melt lenses underlie the ridge axis proximal to the overlapper. Conversely, fissure‐fed sheet flows dominate along the more distal segments, implying the presence of a more continuous axial magma lens. Throughout the survey area, dome abundance increases systematically near second‐order segment boundaries. Within the high abundance zone, some third‐order offsets also correlate with increased dome production, but local peaks in abundance are not tied exclusively to higher‐order ridge offsets. Where dome abundance is low, domes are clustered tightly near second‐order offsets and there is no increase in dome abundance near third‐order segment boundaries.
Orientation of the local interstellar magnetic field inferred from Voyagers' positions
Authors: Ratkiewicz R. , Grygorczuk J.
Published: December 2008

Both Voyagers crossed already the termination shock (TS); Voyager 2 (V2) about 10 AU closer to the Sun than Voyager 1 (V1). The 10 AU difference in the distance reveals the scale of the shock asymmetry. Between several reasons of this asymmetry there is an asymmetric pressure from an interstellar magnetic field. Our goal is to determine what magnetic field strength and orientation produces a 10 AU asymmetry in the TS locations at V1 and V2, when only this factor would be taken into account. Here we show that such a shape of the TS, which would reflect the real positions of V1 and V2 when they crossed it is obtained for the magnetic field vector placed not far from the hydrogen deflection plane with inclination from interstellar flow ∼30°, and for the strength about 3.8 μG. Our predictions are compared with other results.
Sudden, considerable reduction in recent uptake of anthropogenic CO2 by the East/Japan Sea
Authors: Park Geun‐Ha , Lee Kitack , Tishchenko Pavel
Published: December 2008

The East/Japan Sea in the western temperate North Pacific is ventilated from the surface to the bottom over decades. Such short overturning circulation indicates that the anthropogenic CO2 content of the East/Japan Sea is intimately tied to changing surface conditions over similarly short periods. Three surveys in the East/Japan Sea (1992, 1999 and 2007, respectively) have provided a rare opportunity to measure changes in the accumulation rate of anthropogenic CO2 in the East/Japan Sea over the past 15 years in response to changes in surface conditions. We found that the mean uptake rate of anthropogenic CO2 by the East/Japan Sea was 0.3 ± 0.2 mol C m−2 yr−1 for the period 1999–2007, in marked contrast to the rate of 0.6 ± 0.4 mol C m−2 yr−1 for the period 1992–1999. The striking feature is that nearly all anthropogenic CO2 taken up in the more recent period was confined to waters less than 300 m in depth (mean winter mixed layer depth). The rapid and substantial reduction in accumulation in the more recent period is surprising, and is attributed to considerable weakening of overturning circulation, which is responsible for transporting anthropogenic CO2 from the surface to the interior of the East/Japan Sea. This previously undocumented finding may be an indicator of future changes in the global ocean during the coming period of global warming.
Improved estimates of ventilation rate changes and CO2 uptake in the Pacific Ocean using chlorofluorocarbons and sulfur hexafluoride
Authors: Sonnerup Rolf E. , Bullister John L. , Warner Mark J.
Published: December 2008

Depth profiles of dissolved sulfur hexafluoride (SF6) were measured at 10 stations during the 2006 Climate Variability and Predictability (CLIVAR) Repeat Hydrography reoccupation of the 1991 World Ocean Circulation Experiment P16 section along 152°W between 14°S and 52°N. Ventilation ages calculated from the partial pressure of SF6 (pSF6 ages) were generally 6–10 years younger than those calculated from concurrent CFC‐12 partial pressures (pCFC‐12 ages). A one‐dimensional parameterization of transit time distributions is utilized to demonstrate the potential of SF6, as a complement to the CFCs, to constrain the impact of mixing on the tracer‐derived ages. The two‐tracer approach provides an estimate of the mixing‐induced tendency of pCFC‐12 ages to change with time by correcting their bias to younger ages in older waters and their bias to older ages in younger waters. Model scenarios that match both the 2006 pSF6 and pCFC‐12 ages predict a mixing‐induced increase in pCFC‐12 ages of 6–10 years between the 1991 and 2006 occupations of P16, similar to the increase in pCFC‐12 ages observed. Model scenarios tuned to the pCFC‐12 and pSF6 ages from 2006 are used to calculate anthropogenic CO2 along the section and yield slightly smaller anthropogenic CO2 burdens than calculated solely from the pCFC‐12 ages in waters with pCFC‐12 ages >36 years in 2006.
Soil water flux density measurements near 1 cm d−1 using an improved heat pulse probe design
Authors: Kamai Tamir , Tuli Atac , Kluitenberg Gerard J. , Hopmans Jan W.
Published: December 2008

The heat pulse probe (HPP) technique has been successfully applied for estimating water flux density (WFD). Estimates of WFD have been limited to values greater than 10 cm d−1, except for two recent studies with lower detection limits of 2.4 and 5.6 cm d−1. Although satisfactory for saturated soils, it is recognized that current HPP capabilities are limited for applications in the vadose zone, where WFD values are generally below 1 cm d−1. Since numerical sensitivity analysis has shown that large heater needle diameters may increase HPP capabilities in the lower flux density range, a HPP with a 4‐mm‐diameter heater needle was developed and tested. WFD values were obtained by fitting temperature data to the analytical solution for a pulsed cylindrical heat source of infinite length. Effective heater‐thermistor distance and soil thermal diffusivity values were determined for specific heat input scenarios with zero WFD, prior to imposing water flow across the HPP needles. We showed excellent results in the range of 1–10 cm d−1 and satisfactory results in the range of 10–1000 cm d−1.
Coupled cluster calculations for static and dynamic polarizabilities of C60
Authors: Kowalski Karol , Hammond Jeff R. , de Jong Wibe A. , Sadlej Andrzej J.
Published: December 2008

New theoretical predictions for the static and frequency dependent polarizabilities of C60 are reported. Using the linear response coupled cluster approach with singles and doubles and a basis set especially designed to treat the molecular properties in external electric field, we obtained 82.20 and 83.62 Å3 for static and dynamic (λ=1064 nm) polarizabilities. These numbers are in a good agreement with experimentally inferred data of 76.5±8 and 79±4 Å3 [R. Antoine et al., J. Chem. Phys.110, 9771 (1999); A. Ballard et al., J. Chem. Phys.113, 5732 (2000)]. The reported results were obtained with the highest wave function-based level of theory ever applied to the C60 system.
Multiple state transition path sampling
Authors: Rogal Jutta , Bolhuis Peter G.
Published: December 2008

We developed a multiple state transition path sampling (TPS) approach in which it is possible to simultaneously sample pathways connecting a number of different stable states. Based on the original formulation of the TPS we have extended the path ensemble to include trajectories connecting not only two distinct stable states but any two states defined within a system. The multiple state TPS approach is useful in complex systems exhibiting a number of intermediate stable states that are interconnected in phase space. Combining this approach with transition interface sampling we can also directly obtain an expression for the rate constants of all possible transitions within the system.
Correction of spherical aberration for an electrostatic gridded lens
Authors: Pikin Alexander , Kponou Ahovi
Published: December 2008

Two methods to correct spherical aberration in electrostatic gridded lenses have been studied using ray-tracing simulations. Both methods are based on modifying the electrostatic field on the radial periphery of the lens. In the simplest case, the modification is done by extending the grid support axially. In the second method, the electric field on a radial periphery of the lens is modified by applying optimum voltage on an isolated correcting electrode. It is demonstrated that, for a given focal length, the voltage on this lens can be optimized for minimum aberration, and also that these lenses reduce the emittance growth of the ion beam.
Contribution of the electrode-electrolyte interface to the impedance of an electrolytic cell
Authors: Barbero G. , Becchi M. , Freire F. C. M.
Published: December 2008

We analyze the experimental data relevant to samples of solutions of water and KCl, in the shape of slabs of different thicknesses, with electrodes in gold. The experimental data show an increase in the real part of the electrical impedance of the samples in the low frequency region (f∼5 Hz). We compare the theoretical predictions of the models proposed to interpret the anomalous behavior of the resistance of the sample in the dc limit with the experimental data. We show that the theoretical predictions of the models based on the adsorption of ions at the interface and on the Ohmic character of the electrodes are in good agreement with experimental data. The model based on the constant phase element is also considered. However, its agreement with the considered experimental data is very good for what concerns the real part, whereas it is poor for the imaginary part of the electrical impedance. The equivalence between the models based on the adsorption on the electrodes and on the Ohmic character of the electrodes is analyzed. From the good agreement between the two descriptions, a mechanism for the conduction across the electrodes is proposed, according to which the exchange of charge on the electrode takes place in two steps: one related to the adsorption of the ions, and the other connected with their neutralization from the external charges.
Structure and dynamics of empty cages in xenon clathrate hydrate
Authors: Ikeda-Fukazawa Tomoko , Yamaguchi Yohei , Nagashima Kazushige , Kawamura Katsuyuki
Published: December 2008

We performed molecular dynamics calculations of xenon clathrate hydrate to investigate the effects of empty cages on the structure and dynamics of the surrounding lattice. The distinct structure and dynamics of the empty cages, and cages including Xe, which coexist in the lattice, were analyzed. The results show that the ellipsoidal tetrakaidecahedral cage shrinks along the minor ⟨100⟩ axis and expands along the major ⟨100⟩ axis due to the absence of Xe from the cage, whereas the dodecahedral cage shrinks isotropically. These distortions of the empty cages cause a reduction in the lattice constant and an enhancement of the thermal vibrations of the surrounding lattice. The vibrational density of states shows that the hydrogen bonds consisting of the tetrakaidecahedral cage are strengthened by the absence of Xe, whereas those of the dodecahedral cage are weakened. These results show differing mechanisms of guest-host interaction for the two types of cages including Xe. Repulsion is the dominant guest-host interaction for the dodecahedral cage, as proposed by previous studies. For the tetrakaidecahedral cage, however, attractive interaction is dominant along the major ⟨100⟩ axis, whereas repulsive interaction is dominant along the minor ⟨100⟩ axis. The present results suggest that a small number of empty cages can affect not only the local structures but also the macroscopic properties of the crystal. It is concluded that the distortions of the empty cages are one of the important factors governing the density and phase equilibrium of clathrate hydrates.
Single quantum dot emission by nanoscale selective growth of InAs on GaAs: A bottom-up approach
Authors: Patella F. , Arciprete F. , Placidi E. , Fanfoni M. , Balzarotti A. , Vinattieri A. , Cavigli L. , Abbarchi M. , Gurioli M. , Lunghi L. , Gerardino A.
Published: December 2008

We report on single dot microphotoluminescence (μPL) emission at low temperature and low power from InAs dots grown by molecular beam epitaxy in nanoscale holes of a SiO2 mask deposited on GaAs(001). By comparing atomic force microscopy measurements with μPL data, we show that the dot sizes inside the nanoholes are smaller than those of the dots nucleated on the extended GaAs surface. PL of dots spans a wide energy range depending on their size and on the thickness and composition of the InGaAs capping layer. Time-resolved PL experiments demonstrate a negligible loss of radiative recombination efficiency, proving highly effective in the site-controlled dot nucleation.
Terahertz emission from femtosecond laser illuminated (112) surfaces of InSb
Authors: Malevich V. L. , Krotkus A. , Bičiūnas A. , Pačebutas V.
Published: December 2008

Polarized terahertz radiation generated from (112)-oriented InSb surfaces is investigated as a function of the sample azimuthal orientation under excitation from femtosecond Yb:KGW laser pulses. The expressions describing the optical rectification and the surface electric-field-induced optical rectification in reflection from zinc-blende crystals, such as InSb, are calculated. It is shown the contributions of both these effects should be taken into account when describing terahertz emission from InSb surfaces.
X-ray diffraction study of gold nitride films: Observation of a solid solution phase
Authors: Alves L. , Hase T. P. A. , Hunt M. R. C. , Brieva A. C. , Šiller L.
Published: December 2008

The structure of nitride containing gold films produced by reactive ion sputtering and nitrogen plasma etching is investigated using x-ray photoelectron spectroscopy and x-ray diffraction. It is found that gold nitride is a solid solution of nitrogen atoms dissolved in a fcc gold matrix. Differences between the strain and lattice parameters of gold and gold nitride films were observed and are explained by interstitial nitrogen present in the latter.
Gunn oscillations in a self-switching nanodiode
Authors: Xu K. Y. , Wang G. , Song A. M.
Published: December 2008

The feasibility of Gunn oscillations in a planar nanoscale unipolar diode or a self-switching device (SSD) is analyzed using Monte Carlo simulations. The asymmetric nanochannel that the SSD is based on is shown to induce charge domains much more receptively when compared to a reference symmetric nanochannel. The oscillation frequency reaches 130 GHz. Potential applications are discussed in terms of the ease of heat dissipation and generation of oscillations at different frequencies on a single chip, in contrast to a conventional vertical-structure Gunn diode.
Crystalline silicon carbide nanocones and heterostructures induced by released iron nanoparticles
Authors: Liu Zhenyu , Ci Lijie , Srot V. , Jin-Phillipp N. Y. , van Aken Peter A. , Rühle M. , Yang Judith C.
Published: December 2008

We present the formations of crystalline silicon carbide (SiC) nanocones and heterostructures catalyzed by iron nanoparticles, originally encapsulated in graphite-like carbon shells, via the vapor-liquid-solid process. We propose that the nanocone shape is due to the release of iron nanoparticles from their carbon shells followed by agglomeration, where the increasing size of the iron nanoparticle during SiC growth creates the nanocone shape. The release and agglomeration model may explain the formation of multisegmented SiC nanostructures. The encapsulation and controlled release of the metal catalyst is a promising method for the synthesis of unusual one-dimensional nanostructures and complex heterostructures.
Solvent dramatically affects protein structure refinement
Authors: Chopra Gaurav , Summa Christopher M. , Levitt Michael
Published: December 2008

One of the most challenging problems in protein structure prediction is improvement of homology models (structures within 1–3 Å C
α
rmsd of the native structure), also known as the protein structure refinement problem. It has been shown that improvement could be achieved using in vacuo energy minimization with molecular mechanics and statistically derived continuously differentiable hybrid knowledge-based (KB) potential functions. Globular proteins, however, fold and function in aqueous solution in vivo and in vitro. In this work, we study the role of solvent in protein structure refinement. Molecular dynamics in explicit solvent and energy minimization in both explicit and implicit solvent were performed on a set of 75 native proteins to test the various energy potentials. A more stringent test for refinement was performed on 729 near-native decoys for each native protein. We use a powerfully convergent energy minimization method to show that implicit solvent (GBSA) provides greater improvement for some proteins than the KB potential: 24 of 75 proteins showing an average improvement of >20% in C
α
rmsd from the native structure with GBSA, compared to just 7 proteins with KB. Molecular dynamics in explicit solvent moved the structures further away from their native conformation than the initial, unrefined decoys. Implicit solvent gives rise to a deep, smooth potential energy attractor basin that pulls toward the native structure.
Residual stresses, dislocation density and recrystallization process
Authors: Baczmański A. , Wierzbanowski K. , Lipiński P. , Bacroix B. , Lodini A.
Published: December 2008

Residual stress fields induces elastic energy, stored in a material. Another kind of stored energy is due to dislocation density and this energy is mainly localized inside grains. The latter one is considered as a main driving force of recrystallization. However, the stored energy connected with the residual stresses can also have some influence on this process. Both types of energy can be determined experimentally and predicted by deformation models. Using recrystallization models and stored energy distribution, important features of the recrystallization process in cold rolled steel and polycrystalline copper can be explained.
Measuring the influence of magnesium on the elastic anisotropy of aluminum using in situ neutron diffraction
Authors: Ritz Hadas , Dawson Paul , Rogge Ronald
Published: December 2008

Comparison of lattice strains in crystals of various orientations is a primary method of validating polycrystal plasticity simulations. These strains can be measured using in situ neutron diffraction experiments while the corresponding information can be extracted from the simulation results. If the single crystal elastic moduli—particularly the anisotropy of the moduli with respect to lattice direction—are not accurately known, simulations cannot provide a favorable comparison to experiments. Previous work simulating deformation of an aluminum alloy with significant magnesium content (AA-5182) revealed that consistency with the experiments required a higher degree of anisotropy in the elastic moduli in the finite element simulations than that typically reported for pure aluminum. We undertook the current research to determine if the magnesium content causes that larger single crystal elastic anisotropy. Using in situ loading, we measured lattice strains and determined diffraction moduli of materials covering a range of magnesium content. The results show measurable influence of composition on elastic anisotropy.
Neutron diffraction characterisation of thermomechanical behaviour of Fe–Mn–Si shape memory alloy
Authors: Oliver E.C. , Mori T. , Daymond M.R. , Withers P.J.
Published: December 2008

Time-of-flight neutron diffraction profiles were recorded in situ during uniaxial tensile loading and subsequent annealing of an Fe–Mn–Si shape memory alloy. Results are presented on the evolution of phase textures and internal strains. Stress-induced phase transformation occurred preferentially in austenite grains having a 〈110〉 direction aligned axially, and resulted in the formation of ϵ martensite with a {101} fibre texture. These results and the evolution of internal strains are rationalised by consideration of the Schmid factor for the motion of Shockley partial dislocations.
Influence of load on the arrangement of hydroxyapatite crystallites at the interface with implants in different animals
Authors: Benmarouane A. , Taiar R. , Hansen T. , Millet P. , Lodini A.
Published: December 2008

At the interface with an implant, bone tends to change its properties, affecting the acceptance of the implant. The preferred orientation of hydroxyapatite Ca10(PO4)6(OH)2 (HAp) crystallites at the bone–implant interface has been measured with the D20 neutron 2-axis diffractometer at the Institut Max von Laue-Paul Langevin, Grenoble. The implant has two faces, one coated with plasma-sprayed HAp.
Arsenic Toxicity to Saccharomyces cerevisiae Is a Consequence of Inhibition of the TORC1 Kinase Combined with a Chronic Stress Response
Authors: Hosiner Dagmar , Lempiäinen Harri , Reiter Wolfgang , Urban Joerg , Loewith Robbie , Ammerer Gustav , Schweyen Rudolf , Shore David , Schüller Christoph
Published: December 2008

The conserved Target Of Rapamycin (TOR) growth control signaling pathway is a major regulator of genes required for protein synthesis. The ubiquitous toxic metalloid arsenic, as well as mercury and nickel, are shown here to efficiently inhibit the rapamycin-sensitive TORC1 (TOR complex 1) protein kinase. This rapid inhibition of the TORC1 kinase is demonstrated in vivo by the dephosphorylation and inactivation of its downstream effector, the yeast S6 kinase homolog Sch9. Arsenic, mercury, and nickel cause reduction of transcription of ribosome biogenesis genes, which are under the control of Sfp1, a TORC1-regulated transcriptional activator. We report that arsenic stress deactivates Sfp1 as it becomes dephosphorylated, dissociates from chromatin, and exits the nucleus. Curiously, whereas loss of SFP1 function leads to increased arsenic resistance, absence of TOR1 or SCH9 has the opposite effect suggesting that TORC1 has a role beyond down-regulation of Sfp1. Indeed, we show that arsenic activates the transcription factors Msn2 and Msn4 both of which are targets of TORC1 and protein kinase A (PKA). In contrast to TORC1, PKA activity is not repressed during acute arsenic stress. A normal level of PKA activity might serve to dampen the stress response since hyperactive Msn2 will decrease arsenic tolerance. Thus arsenic toxicity in yeast might be determined by the balance between chronic activation of general stress factors in combination with lowered TORC1 kinase activity.
The Knowledge, Attitudes and Usage of Complementary and Alternative Medicine of Medical Students
Authors: DeSylvia Dawn , Stuber Margaret , Fung Cha Chi , Bazargan-Hejazi Shahrzad , Cooper Edwin
Published: December 2008

The increasing use of CAM by patients has led to an increase in teaching about CAM in medical school in the US. In preparation for initiation of a new curriculum in Integrative Medicine at the David Geffen School of Medicine at UCLA a cross sectional survey was used to assess medical students′: (i) familiarity, (ii) opinions, (iii) personal use and (iv) willingness to recommend specific CAM modalities, using a five point Likert scale of an established measure. A total of 263 first, second and third year medical students at UCLA completed surveys. Third year students reported less personal use of CAM and less favorable attitudes towards CAM than first year students. Since this was a cross‐sectional rather than longitudinal study this may be a cohort effect. However, it may reflect the increased curricular emphasis on evidenced‐based medicine, and subsequent student dependence on randomized clinical trials to influence and guide practice. This will need to be addressed in curricular efforts to incorporate Integrative Medicine.
Tissue Specificity and Evolution of Meristematic WOX3 Function
Authors: Shimizu Rena , Ji Jiabing , Kelsey Eric , Ohtsu Kazuhiro , Schnable Patrick S. , Scanlon Michael J.
Published: December 2008

The WUSCHEL-related homeobox (WOX) gene PRESSED FLOWER1 (PRS1) performs a conserved function during lateral organ development in Arabidopsis (Arabidopsis thaliana). Expressed in the periphery of the shoot meristem, PRS1 recruits founder cells that form lateral domains of vegetative and floral organs. Null mutations in PRS1 cause the deletion of lateral stipules from leaves and of lateral sepals and stamens from flowers. Although PRS1 expression is described in the L1 layer, PRS1 recruits founder cells from all meristem layers. The mechanism of non-cell autonomous PRS1 function and the evolution of disparate WOX gene functions are investigated herein. Meristem layer-specific promoters reveal that both L1 and L1-L2 expression of PRS1 fail to fully rescue PRS1 function, and PRS1 protein does not traffic laterally or transversely between shoot meristem layers. PRS1 protein accumulates within all meristematic cell layers (L1-L2-L3) when expressed from the native promoter, presumably due to low-level transcription in the L2 and L3 layers. When driven from the PRS1 promoter, full rescue of vegetative and floral prs1 mutant phenotypes is provided by WUSCHEL1 (WUS1), which is normally expressed in the stem cell organizing center of shoot meristems. The data reveal that WUS1 and PRS1 can engage in equivalent protein-protein interactions and direct transcription of conserved target genes, suggesting that their subfunctionalization has evolved primarily via diverse promoter specificity. Unexpectedly, these results also suggest that meristematic stem cells and lateral organ founder cells are intrinsically similar and formed via equivalent processes such that their ultimate fate is dependent upon stage-specific and domain-specific positional signaling.
Neoparamoebic gill infections: host response and physiology in salmonids
Authors: Powell M. D. , Leef M. J. , Roberts S. D. , Jones M. A.
Published: December 2008

Amoebic gill diseases (AGD) caused primarily by the amphizoic Neoparamoeba spp. have been identified as significant to fish health in intensive aquaculture. These diseases have consequently received significant attention with regard to disease pathophysiology. Neoparamoeba perurans has been putatively identified as the aetiological agent in salmonids, with other species such as turbot Psetta maxima and sea bass Dicentrarchus labrax also affected. Similarly, Neoparamoeba spp. have also been identified in co‐infections with other gill diseases in salmonids. While infection of the gills results in an acute multifocal hyperplastic host response, reduced gill surface area and increased mucous cell densities, ion regulation and respiration in terms of blood gasses are only marginally affected. This may be partially attributed to reserve respiratory capacity and a reduction in mucous viscosity allowing for a greater flushing of the gill, so reducing the gill mucus boundary layer. Clinical and acute infections result in significant cardiovascular compromise with increases in aortic blood pressure, and systemic vascular resistance in Atlantic salmon, Salmo salar, which are not seen in rainbow Oncorhynchus mykiss and brown trout Salmo trutta. Increases in vascular resistance appear to be due to vascular constriction potentially reducing blood flow to the heart in compromised fishes, the overall effect being to lead to a compensatory tissue remodelling and change in cardiac shape in chronically infected fishes. The combined effect of reduced gill surface area and cardiovascular compromise leads to a significant reduction in swimming performance and increases in the routine metabolic rate that lead to an increase in the overall metabolic cost of disease.
Transmission of neozoic Anguillicoloides crassus and established Camallanus lacustris in ruffe Gymnocephalus cernuus
Authors: Unger J. , Brinker A. , Stich H. B.
Published: December 2008

In the present study, groups of ruffe Gymnocephalus cernuus, reared singly, were exposed to defined numbers of Anguillicoloides crassus or Camallanus lacustris under controlled laboratory conditions. Infection took place orally through feeding G. cernuus with axenically cultured and laboratory infected copepods, in which the parasites had developed to the infective third stage (L3). Mean prevalence (94·3%) and infection probability (38·5%) for the established C. lacustris were significantly higher than for the neozoic A. crassus (14·3 and 1·0%, respectively). Peripheral blood leukocytes were significantly increased in infected fish, apparently independent of exposure level, parasite species or intensity of infection compared to the controls. In infected fish, the gonado‐somatic index (IG) was significantly reduced by c. 50%, and the spleen‐somatic index (IS) was significantly increased compared to controls. Both parasites raised similar physiological and immunological responses in G. cernuus, which was able to effectively reject the neozoic A. crassus.
The electric organ discharges of thePetrocephalusspecies (Teleostei: Mormyridae) of the Upper Volta System
Authors: Moritz T. , Engelmann J. , Linsenmair K. E. , Von DerEmde G.
Published: December 2008

In this study, a first comparative investigation of all four species ofPetrocephalus(P. bovei,P. bane,P. soudanensisandP. cf. pallidomaculatus) present in the Upper Volta system and their electric organ discharges (EOD) was conducted. It was found thatP. boveiwas the most widespread (in terms of habitat use), but in several placesP. bovei,P. soudanensisandP. cf. pallidomaculatusoccurred syntopically. All species emitted a triphasic signal, and with very few exceptions, thePetrocephalusspecies of the Upper Volta system could clearly be identified on the basis of their EOD waveforms. The most obvious differences between species in EOD waveforms were in amplitude of the last phase, total duration and fast Fourier transformation (FFT) peak frequency. No sexual dimorphism was present in the EOD of any species although external dimorphism,i.e.an indentation at the base of the anal fin of mature males, was common. The EOD waveform diversity in the Upper Volta principally resembled that found in four sympatricPetrocephalusspecies from the Ogooué system (Gabon) and might play a role in species recognition and speciation processes.
Systematic review: does concurrent therapy with 5‐ASA and immunomodulators in inflammatory bowel disease improve outcomes?
Authors: ANDREWS J. M. , TRAVIS S. P. L. , GIBSON P. R. , GASCHE C.
Published: December 2008

Background With greater use of immunomodulators in inflammatory bowel disease (IBD), it is uncertain whether concurrent therapy with both 5‐aminosalicylic acid [5‐ASA, mesalazine (mesalamine)] and an immunomodulator is necessary.

Aim To determine whether concurrent therapy with both 5‐ASA and immunomodulator(s) improves outcomes in IBD.

Methods Systematic review with search terms ‘azathioprine, 6‐mercaptopurine, thiopurine(s), 5 aminosalicylic acid, mesalazine, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, immunosuppressant(s), immunomodulator and methotrexate’ in November 2007 to identify clinical trials on concurrent 5‐ASA and immunomodulator therapy.

Results Two small controlled studies were found. Neither showed a benefit on disease control beyond immunomodulator monotherapy. Potential pharmacological interactions exist between 5‐ASA and thiopurines. Whilst circumstantial, epidemiological and laboratory evidence suggests that 5‐ASA may assist colorectal cancer (CRC) chemoprevention, it may simply be via anti‐inflammatory effects. With changes in practice, ethical issues and the long lead‐time needed to demonstrate or disprove an effect, no clinical studies can/will directly answer this. The costs of avoiding one CRC in IBD may be as low as 153 times the annual cost of 5‐ASA therapy.

Conclusions It is unclear whether concurrent 5‐ASA and immunomodulator therapy improves outcomes of disease control, drug toxicity or compliance. Concurrent therapy of 5‐ASA and immunomodulators may decrease CRC risk at ‘acceptable’ cost.
Clinically relevant QTc prolongation due to overridden drug–drug interaction alerts: a retrospective cohort study
Authors: Van Der Sijs Heleen , Kowlesar Ravi , Klootwijk A. Peter J. , Nelwan Stefan P. , Vulto Arnold G. , Van Gelder Teun
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• A large number of drugs can prolong the QTc interval on the electrocardiogram (ECG).

• Clinical decision support systems may generate drug safety alerts on QTc prolongation.

• Drug safety alerts are frequently overridden.

WHAT THIS STUDY ADDS

• QTc alert overriding does rarely result in ECG recordings.

• ECGs before and after QTc overrides reveal clinically relevant QTc prolongation.

AIMS To investigate whether, in patients in whom drug–drug interaction (DDI) alerts on QTc prolongation were overridden, the physician had requested an electrocardiogram (ECG), and if these ECGs showed clinically relevant QTc prolongation.

METHODS For all patients with overridden DDI alerts on QTc prolongation during 6 months, data on risk factors for QT prolongation, drug class and ECGs were collected from the medical record. Patients with ventricular pacemakers, patients treated on an outpatient basis, and patients using the low‐risk combination of cotrimoxazole and tacrolimus were excluded. The magnitude of the effect on the QTc interval was calculated if ECGs before and after overriding were available. Changes of the QTc interval in these cases were compared with those of a control group using one QTc‐prolonging drug.

RESULTS In 33% of all patients with overridden QTc alerts an ECG was recorded within 1 month. ECGs were more often recorded in patients with more risk factors for QTc prolongation and with more QTc overrides. ECGs before and after the QTc override were available in 29% of patients. Thirty‐one percent of patients in this group showed clinically relevant QTc prolongation with increased risk of torsades de pointes or ventricular arrhythmias. The average change in QTc interval was +31 ms for cases and −4 ms for controls.

CONCLUSIONS Overriding the high‐level DDI alerts on QTc prolongation rarely resulted in the preferred approach to subsequently record an ECG. If ECGs were recorded before and after QTc overrides, clinically relevant QTc prolongation was found in one‐third of cases. ECG recording after overriding QTc alerts should be encouraged to prevent adverse events.
CD1a expression defines an interleukin-12 producing population of human dendritic cells
Authors: Cernadas M , Lu J , Watts G , Brenner M B
Published: December 2008

Human and murine dendritic cell (DC) subsets are often defined by phenotypic features that predict their functional characteristics. In humans and mice, DC have been shown to have the ability to polarize naive CD4 T cells to a T helper type 1 (Th1) or Th2 phenotype. However, human myeloid DC generated from monocytes (monocyte-derived DC) have often been regarded as a homogeneous population, both phenotypically and functionally. Monocytes give rise to subpopulations of DC in vitro that can be separated on the basis of their expression of CD1a, a well-described DC subset marker. Importantly, we show that the CD1a+ DC subset produces significant quantities of interleukin-12p70 (IL-12p70) upon stimulation and, similar to the murine CD8α+ DC subset, can polarize naive CD4+ T cells to a Th1 phenotype. In contrast, CD1a− DC, similar to murine CD8α− DC, do not produce significant amounts of IL-12p70 upon stimulation or polarize T cells to a Th1 phenotype. Like monocyte-derived DC, CD1a+ and CD1a− DC subsets obtained from CD34+ haematopoietic progenitors under distinct culture conditions were found to have these same features, suggesting that CD1a expression is a marker for myeloid DC that are a major source of IL-12 and Th1 CD4+ T cell polarization in man.
Implications for a role of interleukin-23 in the pathogenesis of chronic gastritis and of peptic ulcer disease
Authors: Koussoulas V , Vassiliou S , Giamarellos-Bourboulis E J , Tassias G , Kotsaki A , Barbatzas C , Tzivras M
Published: December 2008

The present study aimed to investigate the role of gastric mucosa for the secretion of interleukin (IL)-23 in chronic gastritis. One hundred and one patients were enrolled; 47 with duodenal ulcer, 33 with gastric ulcer and 31 with chronic gastritis. Biopsies were incubated in the absence/presence of endotoxins. Supernatants were collected and IL-23 and IL-1β were measured by enzyme-linked immunosorbent assay. Scoring of gastritis was performed according to the updated Sydney score. Patients with duodenal and gastric ulcer and those with chronic gastritis had similar scores of gastritis. IL-23 was higher in supernatants of tissue samples of Helicobacter pylori-positive than of H. pylori-negative patients. No differences were recorded in concentrations of IL-23 and IL-1β between patients with duodenal ulcer, gastric ulcer and chronic gastritis. Positive correlations were found between IL-23 of patients with both duodenal and gastric ulcer and chronic gastritis and the degree of infiltration of neutrophils and monocytes. Similar correlations were observed between IL-23 and IL-1β. IL-23 secreted by the gastric mucosa could be implicated in the pathogenesis of chronic gastritis. IL-23 was released in the presence of H. pylori from the inflamed gastric mucosa and followed the kinetics of IL-1β.
TACI mutations and disease susceptibility in patients with common variable immunodeficiency
Authors: Poodt A E J , Driessen G J A , De Klein A , Van Dongen J J M , Van Der Burg M , De Vries E
Published: December 2008

The most prevalent primary immunodeficiency is common variable immunodeficiency (CVID). Mutations have been described in four genes, ICOS, CD19, BAFF-R and TNFRSF13B (encoding TACI), together associated with 10–15% of CVID cases. We investigated a family with CVID and identified the heterozygous C104R TNFRSF13B mutation in two of the three index-children with CVID, a mother with selective immunoglobulin A deficiency, a mother with recurrent infections and a healthy grandfather. Remarkably, we did not find the TNFRSF13B mutation in the third index-child with CVID, despite his hypogammaglobulinaemia and decreased response to unconjugated pneumococcal vaccine. This family illustrates that TNFRSF13B mutations induce disease susceptibility rather than cause disease directly. Apparently, other genetic or environmental factors, still to be identified, contributed to the development of CVID in this family. Consequently, TNFRSF13B mutations must be interpreted with caution in the clinical setting.
Arterial stiffness in relation to subclinical atherosclerosis
Authors: Wykretowicz A. , Gerstenberger P. , Guzik P. , Milewska A. , Krauze T. , Adamska K. , Rutkowska A. , Wysocki H.
Published: December 2008

Background  Increased arterial stiffness or arteriosclerosis, represents a physiological part of ageing. Atherosclerosis is a process that does not affect the arterial bed uniformly but has a variable local distribution and is frequently superimposed on stiffened vessels. We therefore addressed the question of whether any correlation exists between the general characteristics of arterial stiffness or wave reflection and subclinical atherosclerosis as assessed by carotid intima‐media thickness (IMT) in a sample of healthy subjects.

Methods  A total of 116 healthy subjects (mean age 55 years, 43 female) were evaluated. Arterial stiffness and wave reflection was assessed with the use of digital volume pulse analysis (DVP) and pulse wave analysis (PWA). Subclinical atherosclerosis was assessed by measurement of IMT.

Results  Stiffness Index (SIDVP), the measure of general arterial stiffness correlated significantly with IMT (r = 0·37, P < 0·01). IMT correlated significantly with age (r = 0·5, P < 0·0001), waist to hip ratio (WHR) (r = 0·39, P < 0·0001) and mean blood pressure (BPmean) (r = 0·4, P < 0·0001). IMT did not correlate with measures of wave reflection. SIDVP correlated significantly with age (r = 0·32, P < 0·005), WHR (r = 0·36, P < 0·0001), BPmean (r = 0·36, P < 0·0001) and measurements of wave reflection. However analysis of a model which included variables that significantly influenced SIDVP and IMT, such as age, WHR and mean BP showed that arterial stiffness is not independently associated with subclinical atherosclerosis.

Conclusions  The indices of subclinical atherosclerosis, arterial stiffness and wave reflection, indicate different aspects of vascular status in otherwise healthy subjects
CD31+/Annexin V+ microparticles in healthy offsprings of patients with coronary artery disease
Authors: Bulut D. , Tüns H. , Mügge A.
Published: December 2008

Background  First‐degree relatives of patients with premature coronary artery disease (CAD) develop endothelial dysfunction even in the case they are apparently healthy. In this study we wanted to clarify whether reduced blood levels of circulating endothelial progenitor cells (EPCs), an endogenous repair mechanism to replace dysfunctional endothelium, or elevated endothelial‐derived microparticles (EMPs), an indicator and a mediator of increased endothelial cell damage/apoptosis, are an initial step in the pathogenesis of endothelial dysfunction in genetically predisposed subjects.

Materials and methods  Fifty‐six healthy young men (aged 23 to 31 years) from a fire brigade were enrolled, of which 20 subjects had a positive family history (FH) for premature CAD. Subjects with or without a positive FH did not differ with respect to age, body mass index, risk factors and C‐reactive protein. Endothelial function was assessed by hyperaemia‐mediated relaxation of the brachial artery, blood levels of EPCs (VEGFR2+CD34+ cells) and number of EMPs (CD31+(bright)/Annexin V+ particles) were analysed by flow cytometry.

Results  Hyperaemia‐mediated relaxation of the brachial artery was similar in both groups, and the blood levels of EPCs were comparable. However, the number of EMPs were significantly increased in subjects with a positive FH compared to those with a negative FH (neg. FH: 55·31 ± 4·88 vs. pos. FH: 70·37 ± 6·32 particles µL−1 platelet poor plasma; P < 0·05). Number of EMPs correlate inversely with the FMD response.

Conclusions  These results suggest that increased plasma levels of EMPs may be an initial step in the development of endothelial dysfunction in genetically predisposed subjects.
Stem wood properties of mature Norway spruce after 3 years of continuous exposure to elevated [CO2] and temperature
Authors: KOSTIAINEN KATRI , KAAKINEN SEIJA , SARANPÄÄ PEKKA , SIGURDSSON BJARNI D. , LUNDQVIST SVEN‐OLOF , LINDER SUNE , VAPAAVUORI ELINA
Published: December 2008

The objective of the study was to investigate the interactive effects of elevated atmospheric carbon dioxide concentration, [CO2], and temperature on the wood properties of mature field‐grown Norway spruce (Picea abies (L.) Karst.) trees. Material for the study was obtained from an experiment in Flakaliden, northern Sweden, where trees were grown for 3 years in whole‐tree chambers at ambient (365 μmol mol−1) or elevated [CO2] (700 μmol mol−1) and ambient or elevated air temperature (ambient +5.6 °C in winter and ambient +2.8 °C in summer). Elevated temperature affected both wood chemical composition and structure, but had no effect on stem radial growth. Elevated temperature decreased the concentrations of acetone‐soluble extractives and soluble sugars, while mean and earlywood (EW) cell wall thickness and wood density were increased. Elevated [CO2] had no effect on stem wood chemistry or radial growth. In wood structure, elevated [CO2] decreased EW cell wall thickness and increased tracheid radial diameter in latewood (LW). Some significant interactions between elevated [CO2] and temperature were found in the anatomical and physical properties of stem wood (e.g. microfibril angle, and LW cell wall thickness and density). Our results show that the wood material properties of mature Norway spruce were altered under exposure to elevated [CO2] and temperature, although stem radial growth was not affected by the treatments.