bluuebunny/crossref_metadata_2025 huggingface dataset:
Focused library design in GPCR projects on the example of 5‐HT2c agonists: Comparison of structure‐based virtual screening with ligand‐based search methods
Authors: Bissantz Caterina , Schalon Claire , Guba Wolfgang , Stahl Martin
Published: October 2005

The aim of this study was to investigate the usefulness of structure‐based virtual screening (VS) for focused library design in G protein‐coupled receptors (GPCR) projects on the example of 5‐HT2c agonists. We compared the performance of structure‐based VS against two different homology models using FRED for docking and ScreenScore, FlexX, and PMF for rescoring with the results of 12 ligand‐based similarity searches using four different query compounds and three different similarity metrics (Daylight, FTree, Phacir). The result of the similarity search showed much variation, from an enrichment factor up to 3.2 to worse than random, whereas the structure‐based VS gave a more stable result with a constant enrichment factor around 2. Additionally, actives retrieved by the structure‐based approach were more diverse than the actives among the top scorers of the similarity searches. Based on these results, we suggest basing a focused library design for a GPCR project on a combination of a ligand‐based similarity search and structure‐based docking. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Dielectric and optical properties related to phase transitions in an imidazolium perchlorate [C3N2H5ClO4] crystal
Authors: Czapla Z. , Dacko S. , Kosturek B. , Was’︁kowska A.
Published: October 2005

Structural, dielectric and optical properties of the crystal C3N2H5ClO4 have been studied by X‐ray diffraction, dielec‐tric and birefringence measurements. On cooling, structural phase transitions occurring at 373 K (Tc1) and 210 K (Tc2) are of second and first order, respectively. It is considered from the structure and the dielectric behaviour that Phases I (T > Tc1) and II (Tc2 < T < Tc1) are paraelectric and ferroelectric, respectively, though a hysteresis loop is not found in Phase II. The crystal is destroyed below Tc2 by a large structure deformation. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
High-Dimensional Maximum Marginal Likelihood Item Factor Analysis by Adaptive Quadrature
Authors: Schilling Stephen , Bock R. Darrell
Published: October 2005

Although the Bock–Aitkin likelihood-based estimation method for factor analysis of dichotomous item response data has important advantages over classical analysis of item tetrachoric correlations, a serious limitation of the method is its reliance on fixed-point Gauss-Hermite (G-H) quadrature in the solution of the likelihood equations and likelihood-ratio tests. When the number of latent dimensions is large, computational considerations require that the number of quadrature points per dimension be few. But with large numbers of items, the dispersion of the likelihood, given the response pattern, becomes so small that the likelihood cannot be accurately evaluated with the sparse fixed points in the latent space. In this paper, we demonstrate that substantial improvement in accuracy can be obtained by adapting the quadrature points to the location and dispersion of the likelihood surfaces corresponding to each distinct pattern in the data. In particular, we show that adaptive G-H quadrature, combined with mean and covariance adjustments at each iteration of an EM algorithm, produces an accurate fast-converging solution with as few as two points per dimension. Evaluations of this method with simulated data are shown to yield accurate recovery of the generating factor loadings for models of up to eight dimensions. Unlike an earlier application of adaptive Gibbs sampling to this problem by Meng and Schilling, the simulations also confirm the validity of the present method in calculating likelihood-ratio chi-square statistics for determining the number of factors required in the model. Finally, we apply the method to a sample of real data from a test of teacher qualifications.
A bifunctional Gαi/Gαs modulatory peptide that attenuates adenylyl cyclase activity
Authors: Johnston Christopher A. , Ramer J. Kevin , Blaesius Rainer , Fredericks Zoey , Watts Val J. , Siderovski David P.
Published: October 2005

Signaling via G‐protein coupled receptors is initiated by receptor‐catalyzed nucleotide exchange on Gα subunits normally bound to GDP and Gβγ. Activated Gα · GTP then regulates effectors such as adenylyl cyclase. Except for Gβγ, no known regulators bind the adenylyl cyclase‐stimulatory subunit Gαs in its GDP‐bound state. We recently described a peptide, KB‐752, that binds and enhances the nucleotide exchange rate of the adenylyl cyclase‐inhibitory subunit Gαi. Herein, we report that KB‐752 binds Gαs
· GDP yet slows its rate of nucleotide exchange. KB‐752 inhibits GTPγS‐stimulated adenylyl cyclase activity in cell membranes, reflecting its opposing effects on nucleotide exchange by Gαi and Gαs.
The fuzzy relationship between trawl and acoustic surveys in the North Sea
Authors: Mackinson Steven , van der Kooij Jeroen , Neville Suzanna
Published: October 2005

Adding information on the horizontal and vertical distribution of fish both on and between trawl stations is reason enough to perform acoustic surveys routinely in tandem with annual groundfish trawl surveys. Ideally, acoustic and trawl density indices could be combined to maximize information on fish distribution and provide more reliable estimates of stock size. The core of the problem boils down to the question: “how does what we see on an echosounder relate to what we catch in a net?” The fuzzy logic “model-free estimation” approach presented here sidesteps the need to understand specific mechanisms that determine the nature and variability of any relationship between acoustics and trawl catches. Fuzzy logic models that describe and predict the relationship linking acoustics and environmental variables (inputs) with trawl catches (output) are developed, and the sensitivities and robustness of the approach are discussed. In the models examined, the static environmental variables location and depth proved to be better predictors of trawl catches in the North Sea than the acoustic energy in the first 5 m off the bottom. We suggest that finding the “hidden” relationship between acoustics and trawls will require closer attention to partitioning the acoustics data by species/assemblages and understanding the key gear and behavioural differences responsible for producing the high between-gear variability.
Cultivation and human Impact at 6000 cal yr B.P. in Tropical Lowland Forest at Niah, Sarawak, Malaysian Borneo
Authors: Hunt C.O. , Rushworth G.
Published: October 2005

This paper describes palynological evidence for what appears to be comparatively large-scale human impact in the catchment of the Sungai Niah in the wet tropical lowland swamp forests of Sarawak, Malaysian Borneo close to the Great Cave of Niah. Pollen associated with cleared landscapes and rice cultivation is evident in the sedimentary record from before 6000 cal yr B.P. Human activity seems to have been associated with changes in sedimentary regime, with peat-dominated environments being replaced diachronously by clay-dominated deposition. This may reflect anthropogenic soil erosion in the catchment of the Sungai Niah.
INSURANCE AND OTHER SOCIOECONOMIC DETERMINANTS OF ELDERLY LONGEVITY IN A COSTA RICAN PANEL
Authors: ROSERO-BIXBY LUIS , DOW WILLIAM H. , LACLÉ ADRIANA
Published: October 2005

Official figures show that life expectancy in Costa Rica is longer than in the United States (US), in spite of the fact that per capita health expenditure is only one-tenth that of the US. To check whether this is for real and to explore some of its determinants, 900 Costa Ricans aged 60+ were followed from 1984 to 2001. Follow-up household visits were made, deaths were tracked in the national death registry, and survival status in the voting registry was double-checked. In addition, the survivors were contacted in 2002. Two-thirds of the panel had died by December 2001. Kaplan–Meier curves, life tables and Cox regression were used to analyse the panel’s survival. Mortality in the panel was slightly higher than the Costa Rican average and similar to that in the US, confirming the exceptional longevity of Costa Ricans. Survival was substantially lower among unmarried men and individuals with limited autonomy at the beginning of the study. The effect of socioeconomic status is weak. Insurance effects seem to be confounded by selection biases.
Transcendence Without Reality
Authors: Wright John R.
Published: October 2005

Thomas Nagel has held that transcendence requires attaining a point of view stripped of features unique to our perspective. The aim of transcendence on this view is to get at reality as it is, independent of our contributions to it. I show this notion of transcendence to be incoherent, yet defend a contrasting notion of transcendence. As conceived here, transcendence does not require striving for an external, objective viewpoint on nature or looking at matters from someone else's or an impartial point of view. On my view, which builds on the work of Iris Murdoch, transcendence consists of a refinement of our concepts and sensibility to make them more adequate to the individuals we encounter.
The Place of Pain in Life
Authors: Wyller Truls
Published: October 2005

In his ‘pains and Places’ (Philosophy 78, 2003), John Hyman is right that pains are not located in their causes or effects but in the hurting limbs. However, his position may be consonant with Wittgensteinian expressivism or the view that consciousness is the locus of pain: In producing its own parts, a living organism ‘autopoietically’ sustains itself as an activity functionally present in its limbs. It thus supplies the biological basis for pain consciousness as something wholly present in organs that hurt.
The foraging mode controversy: both continuous variation and clustering of foraging movements occur
Authors: Cooper William E.
Published: October 2005

Ambush and active foraging are held to be discrete foraging modes having important theoretical consequences and evolutionary correlates, but foraging variables (number of movements per minute (MPM) and per cent time spent moving (PTM)) vary continuously. Whether foraging movements are unimodally or bimodally distributed is controversial. Foraging modes have been crucial for understanding taxonomic, morphological, ecological, and behavioural diversification of lizards. Extensive data for them are used to examine the modality‐continuity controversy. MPM and PTM are lognormally distributed, confirming continuity and unimodality. By separating species into groups of ambush and active foragers, bivariate cluster analysis supports the view that lizards fall into active and ambush modes that may reflect adaptive peaks of joint MPM and PTM values. Phylogenetic analysis is needed to test relationships between variables. Although it has greatly advanced understanding of relationships between foraging and other variables, a two‐mode paradigm is too simplistic. Modes defined solely by MPM and PTM may obscure differences in speed and search methods. Overlap between clusters might occur in nearly unstudied major taxa that forage differently. On the MPM×PTM plane connections among ambush, active, and saltatory (start‐stop) foraging are apparent, suggesting that saltatory foragers may occur in lizards. Controversies about continuity, bimodality, and dichotomy of modes are resolved. Clusters represent common combinations of unimodally distributed MPM and PTM occupying limited regions of foraging space. Some species fall outside traditional modes, but examination of correlations between clusters and other variables remains a viable approach.
Perplexing problems of sexual patterns in the fish genus Paralabrax (Serranidae, Serraninae)
Authors: Sadovy Yvonne , Domeier Michael L.
Published: October 2005

For 40 years there have been problems in diagnosing sexual patterns in the serranid genus Paralabrax. Difficulties stem from a combination of factors including terminology, histological and morphological characteristics, and the complex inter‐relationships in the Serranidae between gonad morphology, phylogenetic position and gonad function. A detailed study of four species of Paralabrax: P. maculatofasciatus, P. nebulifer, P. auroguttatus and P. clathratus, clarifies the problems and improves the diagnosis of sexual pattern in the Serranidae, and for similar families that do not have distinct morphologies for primary‐ and secondarily‐derived males. An hypothesis was developed to account for the multiple appearance of gonochorism in the Serranidae, better known for its widespread hermaphroditism.
Simulation of the outer radiation belt electrons near geosynchronous orbit including both radial diffusion and resonant interaction with Whistler‐mode chorus waves
Authors: Varotsou Athena , Boscher Daniel , Bourdarie Sebastien , Horne Richard B. , Glauert Sarah A. , Meredith Nigel P.
Published: October 2005

We present the first simulation results for electrons in the outer radiation belt near geosynchronous orbit, where radial diffusion and resonant interactions with whistler‐mode chorus outside the plasmasphere are taken into account. Bounce averaged pitch‐angle and energy diffusion rates are introduced in the Salammbô code for L ≤ 6.5, for electron energies between 10 keV and 3 MeV and fpe/fce values between 1.5 and 10. Results show that an initial seed population with a power law (Kappa) distribution and a characteristic plasmasheet energy of ∼5 keV can be accelerated up to a few MeV, for 4.5 < L < 6.6 and give a steady state profile similar to the one obtained from average satellite measurements. For a Kp = 4 magnetic storm simulation MeV electron fluxes increase by more than a factor of 10 on a timescale of 1 day. We conclude that whistler‐mode chorus waves can be a major electron acceleration process at geostationary orbit.
Recent elevation changes on the ice streams and ridges of the Ross Embayment from ICESat crossovers
Authors: Smith Benjamin E. , Bentley Charles R. , Raymond Charles F.
Published: October 2005

We analyze differences in ICESat elevation estimates at orbital crossover locations to determine short‐term rates of elevation change for small regions within the Ross Embayment of the West Antarctic Ice sheet. A linear regression of crossover elevation difference against time difference gives an estimate of the mean elevation‐change rate during the ICESat mission to date. We observe prevalent elevation change in the south, with uplift in the upstream end of Kamb Ice Stream at 0.24–0.30 m a−1, and thinning in the parts of Whillans Ice Stream, Mercer Ice Stream, and the adjacent Conway and Engelhardt ice ridges at 0.05–0.18 m a−1. These rates of elevation change are too large to be explained by the 0.02 –0.03 m a−1 formal regression error, by seasonal height variations, or by accumulation‐ or densification‐rate variability, suggesting that they reflect real variations stemming from ice dynamics of the region.
Fully dimensional ab initio description of the structure and energetics of azabenzene-argon complexes
Authors: Makarewicz Jan
Published: October 2005

The structure and energetics of van der Waals complexes of argon with azabenzenes: pyridine, pyrazine, pyrimidine, pyridazine, s-triazine, and s-tetrazine are studied using the second-order Møller-Plesset perturbation theory combined with well-balanced basis sets. The full optimization of the cluster structures and computation of the inter- and intramolecular vibrational frequencies is performed by eliminating the basis set superposition error. The argon equilibrium coordinates are calculated with the accuracy comparable to that reached by standard methods of the structure determination from the spectral data. A simple rule to predict the position of argon with respect to the geometric center of the azabenzene ring is found. The calculated harmonic frequencies of the intermolecular vibrational modes are scaled by the factor of 0.85 to eliminate systematic errors coming from the neglect of anharmonic effects. The scaled frequencies agree with the experimental ones to about 1cm−1, except for pyrimidine-argon and tetrazine-argon for which empirical fundamental frequency estimates are problematic. A simple relation connecting the intermolecular bending frequencies and the monomer quadrupole tensor is found. The perturbation of the monomer properties caused by complexation is analyzed. The modification of the monomer structure by the interaction with argon and its influence on the binding energy appears to be negligible in all complexes studied. However, this interaction affects appreciably the intramolecular modes and causes their frequency shifts. As a consequence, the dissociation energy of the complexes increases by about 5cm−1.
Influence of Lewis number on curvature effects in turbulent premixed flame propagation in the thin reaction zones regime
Authors: Chakraborty Nilanjan , Cant R. S.
Published: October 2005

The influence of differential diffusion on the statistical behavior of the local displacement speed (Sd) in relation to flame curvature is studied based on three-dimensional compressible direct numerical simulations (DNS) of statistically planar flames with single-step Arrhenius-type chemistry. Three different Lewis number cases (Le=0.8, 1.0, and 1.2) are considered. In order to study the influence of differential diffusion on curvature effects in flame propagation, temperature statistics are presented in terms of standard probability density functions (pdfs) and also joint pdfs with curvature for the nonunity Lewis number cases. Temperature statistics are found to be consistent with previous incompressible combustion DNS studies. It is found that both dilatation and tangential strain rate are negatively correlated with curvature. The relative strength of these two correlations determines the nature of the correlation between surface density function (SDF) (∣∇c∣) and curvature. It is also found that the variations of temperature and SDF on an isosurface of reaction progress variable (c) have significant influence on local displacement speed behavior. Displacement speed statistics are presented in terms of standard pdfs as well as joint pdfs with curvature for the three Lewis number cases. The curvature response of the displacement speed and its different components is found to be nonlinear which is consistent with previous two-dimensional DNS with detailed chemistry. The observed nonlinear behavior in the present study in the absence of a detailed chemical mechanism is explained through the influence of differential diffusion.
Insights into fluid tapping-mode atomic force microscopy provided by numerical simulations
Authors: Legleiter Justin , Kowalewski Tomasz
Published: October 2005

In an attempt to understand the physics underlying tapping mode atomic force microscopy (TMAFM) operated in fluids, simulations of complete TMAFM experiments were performed based on a cantilever model invoking the damped driven harmonic oscillator with a single degree of freedom with parameters based on real experiments, the most important of which was a low quality factor (Q). Such a low-Q oscillator captures some of the essential features related to operation of TMAFM in fluids, when compared to real experiments. Fluid TMAFM (a low-Q system) is characterized by a highly anharmonic deflection signal when compared to operation in air (a high-Q system). Our model was able to capture this hallmark of fluid TMAFM without the inclusion of more nuanced hydrodynamic effects. Such modeling can aid in the understanding of tip-sample interactions in fluid TMAFM and in the development of techniques to extract meaningful mechanical surface properties from such interactions.
Optical fabrication of three-dimensional polymeric microstructures
Authors: Cheng Chao-Min , Li Bin , LeDuc Philip R.
Published: October 2005

We present a technique for building three-dimensional structures using optical methods combined with photocuring chemistry. This method merges an optics-based approach with chemical restructuring through the transition of materials from distinct phases. By activating this photocurable material in combination with controlling the intensity distributions that are inherently in optical patterns, in situ fabrication of three-dimensional polymeric microstructures is demonstrated. This experimentally simple approach combined with thermal control can create complex shapes including curved and asymmetric profiles. This method has potential applications in a variety of fields including optical techniques, photoactivatable materials, and laboratory-on-a-chip systems.
Near-red emission from site-controlled pyramidal InGaN quantum dots
Authors: Pérez-Solórzano V. , Gröning A. , Jetter M. , Riemann T. , Christen J.
Published: October 2005

We have fabricated InGaN nanostructures on top of GaN hexagonal pyramids by selective metalorganic vapor-phase epitaxy. With this approach, we are able to exactly control the position of the emitting quantum dot, which is an essential requirement for functionalized single-photon emitters. The emission properties as well as the relaxation and recombination mechanisms were investigated using spectroscopic methods. Regions of different confinement were identified, with the photoluminescence emission from the InGaN quantum dots around 2.03eV and a decay time of 1.4ns. The constant temperature behavior of the radiative decay time confirms its zero-dimensional character. Spatially resolved cathodoluminescence measurements attribute this emission to the apex of the pyramid.
Structure and metal-dependent mechanism of peptidoglycan deacetylase, a streptococcal virulence factor
Authors: Blair David E. , Schüttelkopf Alexander W. , MacRae James I. , van Aalten Daan M. F.
Published: October 2005

Streptococcus pneumoniae
peptidoglycan GlcNAc deacetylase (
Sp
PgdA) protects the Gram-positive bacterial cell wall from host lysozymes by deacetylating peptidoglycan GlcNAc residues. Deletion of the
pgda
gene has been shown to result in hypersensitivity to lysozyme and reduction of infectivity in a mouse model.
Sp
PgdA is a member of the family 4 carbohydrate esterases, for which little structural information exists, and no catalytic mechanism has yet been defined. Here we describe the native crystal structure and product complexes of
Sp
PgdA biochemical characterization and mutagenesis. The structural data show that
Sp
PgdA is an elongated three-domain protein in the crystal. The structure, in combination with mutagenesis, shows that
Sp
PgdA is a metalloenzyme using a His-His-Asp zinc-binding triad with a nearby aspartic acid and histidine acting as the catalytic base and acid, respectively, somewhat similar to other zinc deacetylases such as LpxC. The enzyme is able to accept GlcNAc
3
as a substrate (
K
m
= 3.8 mM,
k
cat
= 0.55 s
-1
), with the
N
-acetyl of the middle sugar being removed by the enzyme. The data described here show that
Sp
PgdA and the other family 4 carbohydrate esterases are metalloenzymes and present a step toward identification of mechanism-based inhibitors for this important class of enzymes.
A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans
Authors: Rétey J. V. , Adam M. , Honegger E. , Khatami R. , Luhmann U. F. O. , Jung H. H. , Berger W. , Landolt H.-P.
Published: October 2005

Slow, rhythmic oscillations (<5 Hz) in the sleep electroencephalogram may be a sign of synaptic plasticity occurring during sleep. The oscillations, referred to as slow-wave activity (SWA), reflect sleep need and sleep intensity. The amount of SWA is homeostatically regulated. It is enhanced after sleep loss and declines during sleep. Animal studies suggested that sleep need is genetically controlled, yet the physiological mechanisms remain unknown. Here we show in humans that a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and SWA during sleep. In contrast, a distinct polymorphism of the adenosine A2Areceptor gene, which was associated with interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers, affects the electroencephalogram during sleep and wakefulness in a non-state-specific manner. Our findings indicate a direct role of adenosine in human sleep homeostasis. Moreover, our data suggest that genetic variability in the adenosinergic system contributes to the interindividual variability in brain electrical activity during sleep and wakefulness.
Conservation and relative importance of residues across protein-protein interfaces
Authors: Guharoy Mainak , Chakrabarti Pinak
Published: October 2005

A core region surrounded by a rim characterizes biological interfaces. We ascertain the importance of the core by showing the sequence entropies of the residues comprising the core to be smaller than those in the rim. Such a distinction is not seen in the 2-fold-related, nonphysiological interfaces formed in crystal lattices of monomeric proteins, thereby providing a procedure for characterizing the oligomeric state from crystal structures of protein molecules. This method is better than those that rely on the comparison of the sequence entropies in the interface and the rest of the protein surface, especially in cases where the surface harbors additional binding sites. To a good approximation there is a correlation between the accessible surface area lost because of complexation and ΔΔ
G
values obtained through alanine-scanning mutagenesis (26-38 cal per Å
2
of the surface buried) for residues located in the core, a relationship that is not discernable for rim residues. If, however, a residue participates in hydrogen bonding across the interface, the extent of stabilization is 52 cal/mol per 1 Å
2
of the nonpolar surface area buried by the residue. As opposed to an amino acid classification used earlier, an environment-based grouping of residues yields a better discrimination in the sequence entropy between the core and the rim.
Proteolysis of Mitotic Chromosomes Induces Gradual and Anisotropic Decondensation Correlated with a Reduction of Elastic Modulus and Structural Sensitivity to Rarely Cutting Restriction Enzymes
Authors: Pope Lisa H. , Xiong Chee , Marko John F.
Published: October 2005

The effect of nonspecific proteolysis on the structure of single isolated mitotic newt chromosomes was studied using chromosome elastic response as an assay. Exposure to either trypsin or proteinase K gradually decondensed and softened chromosomes but without entirely eliminating their elastic response. Analysis of chromosome morphology revealed anisotropic decondensation upon digestion, with length increasing more than width. Prolonged protease treatment resulted only in further swelling of the chromosome without complete dissolution. Mild trypsinization induced sensitivity of chromosome elasticity to five- and six-base-specific restriction enzymes. These results, combined with previous studies of effects of nucleases on mitotic chromosome structure, indicate that mild proteolysis gradually reduces the density of chromatin-constraining elements in the mitotic chromosome, providing evidence consistent with an anisotropically folded “chromatin network” model of mitotic chromosome architecture.
G Protein-coupled Receptor Kinase 2 Negatively Regulates Chemokine Signaling at a Level Downstream from G Protein Subunits
Authors: Jiménez-Sainz M. Carmen , Murga Cristina , Kavelaars Annemieke , Jurado-Pueyo María , Krakstad Beate F. , Heijnen Cobi J. , Mayor Federico , Aragay Anna M.
Published: October 2005

The G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes ligand-activated G protein-coupled-receptors. Here, evidence is shown for a novel role of GRK2 in regulating chemokine-mediated signals. The presence of increased levels of GRK2 in human embryonic kidney (HEK) 293 cells produced a significant reduction of the extracellular signal-regulated kinase (ERK) response to CCL2. This effect is independent of its role in receptor phosphorylation because the kinase-deficient mutant GRK2K220R was able to reduce this response, and ERK activation by CCR2BIX, a phosphorylation-defective receptor mutant, was also inhibited by GRK2. Constructs containing the Gαq-binding RGS-like RH domain of GRK2 or its Gβγ-binding domain could not reproduce the inhibition, thus revealing that GRK2 acts downstream of G proteins. Interestingly, chemokine-driven mitogen-activated protein kinase kinase (MEK) stimulation is not affected in cells overexpressing GRK2 or GRK2K220R or in splenocytes from heterozygous GRK2 mice, where reduced kinase levels correlate with enhanced ERK activation by chemokines. We find GRK2 and MEK in the same multimolecular complex, thus suggesting a mechanism for GRK2 regulation of ERK activity that involves a direct or coordinate interaction with MEK. These results suggest an important role for GRK2 in the control of chemokine induction of ERK activation at the level of the MEK–ERK interface.
The Actin Cytoskeleton Is Required for Selective Types of Autophagy, but Not Nonspecific Autophagy, in the YeastSaccharomyces cerevisiae
Authors: Reggiori Fulvio , Monastyrska Iryna , Shintani Takahiro , Klionsky Daniel J.
Published: October 2005

Autophagy is a catabolic multitask transport route that takes place in all eukaryotic cells. During starvation, cytoplasmic components are randomly sequestered into huge double-membrane vesicles called autophagosomes and delivered into the lysosome/vacuole where they are destroyed. Cells are able to modulate autophagy in response to their needs, and under certain circumstances, cargoes such as aberrant protein aggregates, organelles and bacteria can be selectively and exclusively incorporated into autophagosomes. In the yeast Saccharomyces cerevisiae, for example, double-membrane vesicles are used to transport the Ape1 protease into the vacuole, or for the elimination of superfluous peroxisomes. In the present study we reveal that in this organism, actin plays a role in these two types of selective autophagy but not in the nonselective, bulk process. In particular, we show that precursor Ape1 is not correctly recruited to the PAS, the putative site of double-membrane vesicle biogenesis, and superfluous peroxisomes are not degraded in a conditional actin mutant. These phenomena correlate with a defect in Atg9 trafficking from the mitochondria to the PAS.
Stable Ribosome Binding to the Endoplasmic Reticulum Enables Compartment-specific Regulation of mRNA Translation
Authors: Stephens Samuel B. , Dodd Rebecca D. , Brewer Joseph W. , Lager Patrick J. , Keene Jack D. , Nicchitta Christopher V.
Published: October 2005

In eukaryotic cells, protein synthesis is compartmentalized; mRNAs encoding secretory/membrane proteins are translated on endoplasmic reticulum (ER)-bound ribosomes, whereas mRNAs encoding cytosolic proteins are translated on free ribosomes. mRNA partitioning between the two compartments occurs via positive selection: free ribosomes engaged in the translation of signal sequence-encoding mRNAs are trafficked from the cytosol to the ER. After translation termination, ER-bound ribosomes are thought to dissociate, thereby completing a cycle of mRNA partitioning. At present, the physiological basis for termination-coupled ribosome release is unknown. To gain insight into this process, we examined ribosome and mRNA partitioning during the unfolded protein response, key elements of which include suppression of the initiation stage of protein synthesis and polyribosome breakdown. We report that unfolded protein response (UPR)-elicited polyribosome breakdown resulted in the continued association, rather than release, of ER-bound ribosomes. Under these conditions, mRNA translation in the cytosol was suppressed, whereas mRNA translation on the ER was sustained. Furthermore, mRNAs encoding key soluble stress proteins (XBP-1 and ATF-4) were translated primarily on ER-bound ribosomes. These studies demonstrate that ribosome release from the ER is termination independent and identify new and unexpected roles for the ER compartment in the translational response to induction of the unfolded protein response.
Colloidal Stability and Titania Precipitate Morphology: Influence of Short‐Range Repulsions
Authors: Look J.‐L. , Zukoski C. F.
Published: October 2005

For a wide range of reagent concentrations, particles formed from the hydrolysis of tetraethyl orthotitanate in aqueous ethanol solutions fall into two morphological types. In the first, the particles are composed of uniform spheres, while in the second, the precipitate consists of agglomerates of discrete particles which have been fused together by further reaction products. To explain this observation, we develop a growth mechanism where colloidal stability is imparted to the growing particles through a combination of electrostatic and short‐range repulsions giving rise to a shallow secondary minimum which develops for certain particle sizes and results in the formation of doublets that can be fused together. If the particle surface potential is of sufficient magnitude, the secondary minimum is no longer accessible by Brownian motion and uniform precipitates result. The effects of particle surface potential and reaction medium ionic strength are discussed.
Formation and Microstructure of Carbon‐Containing Oxide Scales by Oxidation of Single Crystals of Zirconium Carbide
Authors: Shimada Shiro , Nishisako Masaru , Inagaki Michio , Yamamoto Kazuhide
Published: October 2005

The isothermal oxidation of ZrC single crystals with (100) orientation was carried out at temperatures of 500°, 550°, and 600°C at an oxygen pressure of 2.6 kPa for times up to 240 h. A polished cross section of the oxidized crystal was observed by backscattered electron imaging in a scanning electron microscope. Quantitative chemical analysis for Zr, O, and C and their elemental profiles by the linescan method in the ZrC and oxide scale were performed by wavelength dispersive X‐ray microanalysis. A thin foil of a crystal oxidized at 600°C was examined by transmission electron microscopy. It was found that the oxide scale was divided into two regions, zones 1 and 2, which contained 14 to 23 and 7 to 10 at. % carbon, respectively. Zone 1 exhibited an almost compact, pore‐free matrix of c‐ZrO2. In zone 2, some growth and aggregation of the c‐ZrO2 occurred, producing 5‐ to 20‐nm‐sized particles between which carbon should have been present. The thickness of zone 1 increased parabolically up to 240 h at 500°C and probably in an early period at 550° and 600°C, reaching a constant (about 2 (μm), in contrast to the thickness of zone 2, which increased linearly with time.
Silicon Carbide/Calcium Aluminosilicate: A Notch‐Insensitive Ceramic‐Matrix Composite
Authors: Cady Carl M. , Mackin Thomas J. , Evans Anthony G.
Published: October 2005

Tension experiments performed on a 0/90 laminated silicon carbide/calcium aluminosilicate composite at room temperature establish that this material is notch insensitive. Multiple matrix cracking is determined to be the stress redistribution mechanism. This mechanism is found to provide a particularly efficient means for creating local inelastic strains, which eliminate stress concentrations.
Microstructure and Mechanical Properties of SiC Platelet/Cordierite Glass‐Ceramic Composites
Authors: Chaim Rachman , Talanker Vladimir
Published: October 2005

Cordierite glass‐ceramics reinforced with different volume fractions (0, 10, 20, and 30%) of SiC platelets were fabricated by mechanically mixing appropriate powders and hot pressing above the glass transition temperature. Some of the specimens were subjected to postsintering crystallization treatments. The resultant sintered microstructure was textured, and within it the SiC platelets tended to be oriented with their basal planes perpendicular to the hot‐pressing direction. The bending strength of the hot‐pressed specimens was constant, while the fracture toughness increased with the SiC content. Crystallization heat treatment in argon for 30 min at 1200°C caused a significant decrease in the bending strength, but improved the fracture toughness. Fractography has confirmed the crack deflection to be a dominant mechanism in the crystallized specimens, which contributes to the improvement in the fracture toughness. The overall changes in the mechanical properties are discussed with respect to the change in the residual stresses and oxidation characteristics of the SiC platelets.
Measurement of Indentation Residual Stresses in Materials Susceptible to Slow Crack Growth
Authors: Salomonson Jonas , Rowcliffe David
Published: October 2005

Knowledge of the size and distribution of the indentation residual stress field is important when interpreting slow crack growth data for indented ceramic materials. A technique based on compressively loading indentation cracks has been used to measure the wedging residual stresses at radial indentation cracks. The method also gives information on the fatigue limit and can be applied on any ceramic material susceptible to slow crack growth. Soda–lime glass specimens were indented and the resulting residual stresses, wedging the radial cracks, were measured as a function of indentation load. Calculations of K0, the fatigue limit, were made for both virgin indentation cracks and cracks aged until saturation. The magnitude of closing stress needed to prevent slow crack growth was found to depend linearly on the indentation load. For example, for indentation loads of 20 and 60 N, the corresponding closing stresses were 14 and 26 MPa, respectively.
Modification of Piezoelectric Characteristics of the Pb(Mg,Nb)O3‐PbZrO3‐PbTiO3 Ternary System by Aliovalent Additives
Authors: Shaw Jin‐Chen , Liu Kuo‐Shung , Lin I‐Nan
Published: October 2005

The effects of donor and acceptor doping on the piezoelectric properties of 18Pb(Mg1/3Nb2/3)O3·39PbZrO3·43PbTiO3ternary solid solution have been investigated. The dopants influence in a pronounced way both the crystal structure and microstructure of the materials. The materials are transformed from the rhombohedral to the tetragonal structure, and the grain size is reduced when Nb5+ cations are added. The crystal structures are transformed from the rhombohedral to the cubic structure, and grain growth is enhanced, when Mg2+ cations are included. The values of KP and K are maximized for 1‐mol%‐Nb5+‐doped samples (KP= 0.69, K= 1152); the Qm factor and Ec are optimized for 4‐mol%‐Mg2+‐doped samples (Qm= 1534, Ec= 0.56).
Water Corrosion Behavior of Fluoroaluminate Glass
Authors: Dai Yisheng , Takahashi Katsuo , Yamaguchi Ichirou
Published: October 2005

The water corrosion behavior of a typical fluoroaluminate glass was studied in both plate and powder form. The infrared spectra of the corroded plate sample exhibited an overall transmittance decrease but little absorption at 3450 cm–1. Transmittance in the visible region was substantially reduced with an increase of haziness. Microscopic observation revealed a uniform corrosion of the glass surface without any detectable cracks. Dissolution of the glass powder in water resulted in a slight pH increase of the solution. The leaching was congruent and the dynamic dissolution process monitored by solution conductivity followed a logarithmic correlation with time. The corrosion behavior was greatly different from that of fluoride glasses in other systems.
Thermodynamic Assessment of the CaO–MgO–Al2O3 System
Authors: Hallstedt Bengt
Published: October 2005

The system CaO–MgO–Al3O3 has been assessed with the Calphad technique using a computerized optimization procedure called parrot. The rather meager experimental information, mainly on liquidus relations, is described reasonably well, but the lack of data, especially on solid‐phase relations, implies that the present assessment should be regarded as provisional. The system contains one stable ternary phase with the stoichiometry 3CaO·2Al2O3·MgO.
Enhanced Machinability of Silicon Carbide via Microstructural Design
Authors: Padture Nitin P. , Evans Christopher J. , Xu Hockin H. K. , Lawn Brian R.
Published: October 2005

The machinability of a heterogeneous silicon carbide with weak interphase boundaries, elongated grains, and high internal stresses is evaluated relative to a homogeneous control material with a well‐bonded, equiaxed, and unstressed grain structure. Drilling and grinding rates for the silicon carbide are substantially enhanced by the microstructural heterogeneity—the weak boundaries enable easy grain‐scale dislodgement in place of the more conventional macrofracture chipping mode of removal. At the same time, the residual machining damage in the machined surfaces is significantly less strength degrading in the heterogeneous material. Implications concerning the microstructural design of flaw‐tolerant ceramics for enhanced machinability are considered.
Dispersion of Thermooptic Coefficients of Soda–Lime–Silica Glasses
Authors: Ghosh Gorachand
Published: October 2005

The thermooptic coefficients, i.e., the variation of refractive index with temperature (dn/dT), are analyzed in a physically meaningful model for two series of soda–lime–silica glasses, 25Na2O·xCaO·(75 –x)SiO2 and (25 –x)Na2O·xCaO·75SiO2. This model is based on three physical parameters—the thermal expansion coefficient and excitonic and isentropic optical bands that are in the vacuum ultraviolet region—instead of on consideration of the temperature coefficient of electronic polarizability, as suggested in 1960. This model is capable of predicting and analyzing the thermooptic coefficients throughout the transmission region of the optical glasses at any operating temperature.
Role of Fiber Stitching in Eliminating Transverse Fracture in Cross‐Ply Ceramic Composites
Authors: Lu Tian‐Jian , Hutchinson John W.
Published: October 2005

A theoretical study of the feasibility of using fiber stitching to prevent transverse matrix cracking in cross‐ply ceramic composites is reported. The prototype problem solved is a curved composite beam subject to pure bending (the C‐specimen), which develops a transverse tensile stress σ0 acting across its circumferential midplane. Fiber stitches normal to this plane bridge a circumferential matrix crack lying along the midplane of the specimen. Results are presented for the energy release rate of this matrix crack as a function of a nondimensional parameter characterizing the fiber stitches. Sufficiently large values of this parameter ensure the applicability of the classical ACK (Aveston, Cooper and Kelly) limit for a steady‐state matrix crack subject to σ0. The results obtained can be used to choose the level of stitching such that transverse matrix cracking will be excluded.
Strength and Young's Modulus Behavior of a Partially Sintered Porous Alumina
Authors: Nanjangud Savitha C. , Brezny Rasto , Green David J.
Published: October 2005

The strength of alumina materials that had been subjected to varying degrees of densification was determined. Significant increases in strength were obtained for these materials even when there was minimal densification. For the most porous materials, the Weibull modulus values were similar but showed a significant increase for materials that were close to the theoretical density. Young's modulus data were found to be similar to previous work, in that significant increases occur during the initial stage of sintering, showing a strong correlation with the strength data. A simple modi fication to a previous theory allowed the Young's modulus data to be fitted with excellent accuracy.
Calcium Silicate Carbonation Products
Authors: Goto Seishi , Suenaga Kenzo , Kado Takeshi , Fukuhara Minoru
Published: October 2005

calcium silicates such as C3S, βT‐C2S, and γgM‐C2S† were carbonated under saturated humidity at room temperature. Carbonation products were examined by DT‐TGA, gasphase mass spectroscopy, and XRD. Two types of carbonate were produced: one type, which was rather poorly crystallized, was decarbonated at a very low temperature, below 600°C; the other type was a crystalline phase such as calcite, aragonite, and/or vaterite which was decarbonated above 600°C. The data were compared to existing data for calcium carbonates and basic calcium carbonates. The results suggest that an amorphous calcium silicate hydrocarbonate was one of the carbonation products which formed during the hydration/carbonation reaction.
Novel Processing of 1‐3 Piezoelectric Ceramic/Polymer Composites for Transducer Applications
Authors: McNulty Thomas F. , Janas Victor F. , Safari Ahmad , Loh Roland L. , Cass Richard B.
Published: October 2005

Piezoelectric ceramic/polymer composites with 1‐3 connectivity were made by weaving sized lead zirconate titanate (PZT) fiber bundles through a honeycomb support. Bundles comprised of fine‐scale, 20‐50 μm green fibers, made using the viscous suspension spinning process, were sized to increase their manageability. The sizing step comprised of soaking the green PZT fiber bundles in an aqueous solution of poly(vinyl alcohol), then pulling the wet fibers through a steel sizing die. Sizing resulted in dense and flexible fiber bundles, which facilitated composite construction and led to composites with increased volume fractons. Sintering, polymer embedding, and machining produced a composite exhibiting 1‐3 connectivity. Composites with 10 vol% PZT yilded d33 values of 230 pC/N and a dielectric constant of 130.
MoSi2‐Based Sandwich Composite Made by Tape Casting
Authors: Tuffé Stephane , Wilkinson David S.
Published: October 2005

The mechanical properties of a novel laminar composite made by tape casting have been studied. The composite consists of three layers in which an inner core of pure molybdenum disilicide (MoSi2) is sandwiched between two layers of MoSi2 reinforced with alumina platelets. Monolithic MoSi2 exhibits poor room‐temperature strength and a brittle indentation strength response, indicative of the absence of R‐curve behavior. The flexural behavior of the sandwich composite (both strength and toughness) is dominated by the properties of the outer layer, so long as the thickness of this layer exceeds a critical value. A model has been developed which successfully predicts the critical thickness required.
Preparation of Metal Ruthenates by Spray Pyrolysis
Authors: Senzaki Yoshihide , Hampden‐Smith Mark J. , Kodas Toivo T. , Hussler John W.
Published: October 2005

Submicrometer crystalline metal ruthenate powders with perovskite structure, MRuO3 (M = Sr, La), and pyrochlore structure, M2Ru2O7‐x(0.5 < x < 1; M = Bi, Pb, Y, Eu, Gd, Tb, Dy, Ho, Er, Tm), were prepared by spray pyrolysis using metal nitrates and glycolates under an oxygen‐gas atmosphere at temperatures up to 1100°C. Submicrometer‐sized solid single crystals (SrRuO3), submicrometer‐sized hollow spheres consisting of nanocrystallites (pyrochlore rare‐earth ruthenates, Bi2Ru2O7, and Pb2Ru2O6.5 below 1000°C), and nanometer‐sized particles (Pb2.31Ru1.69O6.5 and Bi‐Pb‐O above 1000°C) were observed. Particle formation proceeded by intraparticle reaction and intraparticle reaction followed by evaporation of volatile metal oxides to form metal oxide vapors followed by condensation and reaction to form particles. The former was observed for systems where no volatile metal oxides were formed, whereas the latter occurred for the Pb‐Ru‐O and Bi‐Ru‐O systems, where volatile metal oxides, such as Bi2O, PbO, and RuOx could occur. Particle morphology depended strongly on precursor properties. Submicrometer‐sized single‐crystal SrRuO3 particles could be formed from the metal nitrates but not from Sr(NO3)2 and ruthenium glycolate, which gave hollow polycrystalline particles. In general, crystallite size could be controlled by varying precursor properties and reactor temperature, with higher temperatures giving larger crystallite sizes.