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Selected AbstractsStrong irritants masquerading as skin allergens: the case of benzalkonium chlorideCONTACT DERMATITIS, Issue 4 2004David A. Basketter Chemicals may possess a number of hazards to human health including the ability to cause skin irritation and contact allergy. Identification and characterization of these properties should fall within predictive toxicology, but information derived from human exposure, including clinical experience, is also of importance. In this context, it is of interest to review the case of benzalkonium chloride, a cationic surfactant. This chemical is a well-known skin irritant, but on occasions it has also been reported to have allergenic properties, typically on the basis of positive diagnostic patch test data. Because the accumulated knowledge concerning the properties of a chemical is employed as the basis for its regulatory classification (e.g. in Europe), as well as for informing the clinical community with respect to the diagnosis of irritant versus allergic contact dermatitis (ACD), it is important to distinguish properly which chemicals are simply irritants from those which are both irritant and allergenic on skin. A review of the information on benzalkonium chloride confirms that it is a significant skin irritant. However, both predictive test results and clinical data lead to the conclusion that benzalkonium chloride is, at most, an extremely rare allergen, except perhaps in the eye, but with many supposed cases of ACD being likely to arise from the misinterpretation of patch test data. As a consequence, this substance should not normally be regarded as, or classified as, a significant skin sensitizer. [source] Multilevel structure of reinforcing silica and carbonJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 3-1 2000D.W. Schaefer Using small-angle x-ray (SAXS), neutron (SANS), x-ray diffraction and light scattering, we study the structure of colloidal silica and carbon on length scales from 4 Å < q,1 < 107 Å where q is the magnitude of the scattering vector. These materials consist of primary particles of the order of 100 Å, aggregated into micron-sized aggregates that in turn are agglomerated into 100 µ agglomerates. The diffraction data show that the primary particles in precipitated silica are composed of highly defective amorphous silica with little intermediate-range order (order on the scale of several bond distances). On the next level of morphology, primary particles arise by a complex nucleation process in which primordial nuclei briefly aggregate into rough particles that subsequently smooth out to become the seeds for the primaries. The primaries aggregate to strongly bonded clusters by a complex process involving kinetic growth, mechanical disintegration and restructuring. Finally, the small-angle scattering (SAS) data lead us to postulate that the aggregates cluster into porous, rough-surfaced, non-mass-fractal agglomerates that can be broken down to the more strongly bonded aggregates by application of shear. We find similar structure in pelletized carbon blacks. In this case we show a linear scaling relation between the primary and aggregate sizes. We attribute the scaling to mechanical processing that deforms the fractal aggregates down to the maximum size able to withstand the compaction stress. Finally, we rationalize the observed structure based on empirical optimization by filler suppliers and some recent theoretical ideas due to Witten, Rubenstein and Colby. [source] Antimicrobial peptide interactions with silica bead supported bilayers and E. coli: buforin II, magainin II, and arenicin,JOURNAL OF PEPTIDE SCIENCE, Issue 8 2009Ryan W. Davis Abstract Using the unique quantitative capabilities of hyperspectral confocal microscopy combined with multivariate curve resolution, a comparative approach was employed to gain a deeper understanding of the different types of interactions of antimicrobial peptides (AMPs) with biological membranes and cellular compartments. This approach allowed direct comparison of the dynamics and local effects of buforin II, magainin II, and arenicin with nanoporous silica bead supported bilayers and living E. coli. Correlating between experiments and comparing these responses have yielded several important discoveries for pursuing the underlying biophysics of bacteriocidal specificity and the connection between structure and function in various cellular environments. First, a novel fluorescence method for direct comparison of a model and living system is demonstrated by utilizing the membrane partitioning and environmental sensitivity of propidium iodide. Second, measurements are presented comparing the temporal dynamics and local equilibrium concentrations of the different antimicrobial agents in the membrane and internal matrix of the described systems. Finally, we discuss how the data lead to a deeper understanding of the roles of membrane penetration and permeabilization in the action of these AMPs. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Raman scattering study of adsorption/desorption of water from single-walled carbon nanotubesJOURNAL OF RAMAN SPECTROSCOPY, Issue 8 2005Suresh C. Sharma Abstract We utilized Raman spectroscopy to investigate H2O adsorption in and desorption from single-walled carbon nanotubes (SWCNTs). SWCNT tips were opened by known chemical methods and H2O was inserted into the tubes via capillary action over periods up to 136 h. The wavenumbers in the OH bending region of H2O increase almost exponentially with H2O treatment time. Following H2O adsorption for 136 h, Raman spectra were also measured as a function of heat-treatment temperature. These data lead to 0.07 eV for the H2O desorption energy from SWCNTs. Copyright © 2005 John Wiley & Sons, Ltd. [source] Evolution of the Respiratory System in Nonavian Theropods: Evidence From Rib and Vertebral MorphologyTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 9 2009Emma R. Schachner Abstract Recent reports of region-specific vertebral pneumaticity in nonavian theropod dinosaurs have brought attention to the hypothesis that these animals possessed an avian-style respiratory system with flow-through ventilation. This study explores the thoracic rib and vertebral anatomy of Sinraptor, Allosaurus, Tyrannosaurus, and Deinonychus; four nonavian theropods that all show well-preserved thoracic vertebrae and ribs. Comparisons to the osteology and soft tissue anatomy of extant saurians provide new evidence supporting the hypothesis of flow-through ventilation in nonavian theropods. Analyses of diapophyseal and parapophyseal position and thoracic rib morphology suggest that most nonavian theropods possessed lungs that were deeply incised by the adjacent bicapitate thoracic ribs. This functionally constrains the lungs as rigid nonexpansive organs that were likely ventilated by accessory nonvascularized air sacs. The axial anatomy of this group also reveals that a crocodilian-like hepatic-piston lung would be functionally and biomechanically untenable. Taken together with the evidence that avian-like air sacs were present in basal theropods, these data lead us to conclude that an avian-style pulmonary system was likely a universal theropod trait. Anat Rec, 292:1501,1513, 2009. 2009. © 2009 Wiley-Liss, Inc. [source] Marginal Analysis of Incomplete Longitudinal Binary Data: A Cautionary Note on LOCF ImputationBIOMETRICS, Issue 3 2004Richard J. Cook Summary In recent years there has been considerable research devoted to the development of methods for the analysis of incomplete data in longitudinal studies. Despite these advances, the methods used in practice have changed relatively little, particularly in the reporting of pharmaceutical trials. In this setting, perhaps the most widely adopted strategy for dealing with incomplete longitudinal data is imputation by the "last observation carried forward" (LOCF) approach, in which values for missing responses are imputed using observations from the most recently completed assessment. We examine the asymptotic and empirical bias, the empirical type I error rate, and the empirical coverage probability associated with estimators and tests of treatment effect based on the LOCF imputation strategy. We consider a setting involving longitudinal binary data with longitudinal analyses based on generalized estimating equations, and an analysis based simply on the response at the end of the scheduled follow-up. We find that for both of these approaches, imputation by LOCF can lead to substantial biases in estimators of treatment effects, the type I error rates of associated tests can be greatly inflated, and the coverage probability can be far from the nominal level. Alternative analyses based on all available data lead to estimators with comparatively small bias, and inverse probability weighted analyses yield consistent estimators subject to correct specification of the missing data process. We illustrate the differences between various methods of dealing with drop-outs using data from a study of smoking behavior. [source] Branched KLVFF Tetramers Strongly Potentiate Inhibition of ,-Amyloid AggregationCHEMBIOCHEM, Issue 15 2007Sidhartha M. Chafekar Abstract The key pathogenic event in the onset of Alzheimer's disease (AD) is the aggregation of ,-amyloid (A,) peptides into toxic aggregates. Molecules that interfere with this process might act as therapeutic agents for the treatment of AD. The amino acid residues 16,20 (KLVFF) are known to be essential for the aggregation of A,. In this study, we have used a first-generation dendrimer as a scaffold for the multivalent display of the KLVFF peptide. The effect of four KLVFF peptides attached to the dendrimer (K4) on A, aggregation was compared to the effect of monomeric KLVFF (K1). Our data show that K4 very effectively inhibits the aggregation of low-molecular-weight and protofibrillar A,1,42 into fibrils, in a concentration-dependent manner, and much more potently than K1. Moreover, we show that K4 can lead to the disassembly of existing aggregates. Our data lead us to propose that conjugates that bear multiple copies of KLVFF might be useful as therapeutic agents for the treatment of Alzheimer's disease. [source] Latent class models for use of primary care: evidence from a British panelHEALTH ECONOMICS, Issue 9 2005Teresa Bago d'Uva Abstract This paper models access to and utilisation of primary care using data from the British Household Panel Survey for the period 1991,2001. A latent class panel data framework is adopted to model individual unobserved heterogeneity in a flexible way. Accounting for the panel structure of the data leads to a substantial improvement in fit, and permits the identification of latent classes of users of health care. Analysis by gender shows that men and women respond differently to some factors, in particular, to age and income. There is evidence of a positive impact of income on the probability of seeking primary care. This effect is especially significant in the case of women. For both genders, the marginal effect of income on the propensity to visit a GP is greater for individuals who are less likely to seek primary care. A latent class aggregated count data model for the number of GP visits classifies individuals in three latent classes and shows a positive income effect particularly amongst those with lower levels of utilisation. Copyright © 2005 John Wiley & Sons, Ltd. [source] Assembly, tuning, and transfer of action systems in infants and robotsINFANT AND CHILD DEVELOPMENT, Issue 1 2008Luc Berthouze Abstract This paper seeks to foster a discussion on whether experiments with robots can inform theory in infant motor development and specifically (1) how the interactions among the parts of a system, including the nervous and musculoskeletal systems and the forces acting on the body, induce organizational changes in the whole, and (2) how exploratory behaviour and selective informational signals at the timescale of skill learning may allow behaviour to become stabilized at the longer timescale of development. The paper describes how three generative principles, inspired from developmental biology and shown to underlie the dynamics of infants learning to bounce in a Jolly Jumper, were broken into a set of mechanisms suitable for controlling a robotic system and resulted in a similar developmental profile. A comparison of infant and robot data leads to a set of criteria for improving the usefulness of robotic studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] Crystalline/Crystalline Phase Transitions in Polymer Systems Consisting of Finite-Size Crystals in Each Crystalline Phase: Generalized Gibbs-Thomson EquationMACROMOLECULAR THEORY AND SIMULATIONS, Issue 7 2010Matsuo Hirami Abstract For polymer systems of two crystalline phases of one polymer component, each phase being consisted of polymer crystals of a finite size, we derive the crystalline-crystalline phase transition relationship, i.e., generalized Gibbs-Thomson equation. Its application combined with the crystalline-liquid transition relationship (usual Gibbs-Thomson equation) to the phase behavior of PT phase diagram of polyethylene (PE) is investigated, where the orthorhombic-hexagonal phase transition of PE crystal under high pressure being involved. Comparison with experimental data leads to the estimates of the structural characteristics such as the ratios of (the end surface free energy of polymer crystal/crystal length) for the respective crystalline phases. [source] 15N relaxation study of the amyloid ,-peptide: structural propensities and persistence lengthMAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2006Jens Danielsson Abstract The dynamics of monomeric Alzheimer A,(1,40) in aqueous solution was studied using heteronuclear NMR experiments. 15N NMR relaxation rates of amide groups report on the dynamics in the peptide chain and make it possible to estimate structural propensities from temperature-dependent relaxation data and chemical shifts change analysis. The persistence length of the polypeptide chain was determined using a model in which the influence of neighboring residue relaxation is assumed to decay exponentially as a function of distance. The persistence length of the A,(1,40) monomer was found to decrease from eight to three residues when temperature was increased from 3 to 18 °C. At 3 °C the peptide shows structural propensities that correlate well with the suggested secondary structure regions of the peptide to be present in the fibrils, and with the ,-helical structure in membrane-mimicking systems. Our data leads to a structural model for the monomeric soluble ,-peptide with six different regions of secondary structure propensities. The peptide has two regions with ,-strand propensity (residues 16,24 and 31,40), two regions with high PII-helix propensity (residues 1,4 and 11,15) and two unstructured regions with higher mobility (residues 5,10 and 25,30) connecting the structural elements. Copyright © 2006 John Wiley & Sons, Ltd. [source] Grapevine productivity and yield components: A case study using field vines of Zante currantAUSTRALIAN JOURNAL OF GRAPE AND WINE RESEARCH, Issue 2 2004JOHN A. CONSIDINE Abstract Yield components of the parthenocarpic cultivar Zante were analysed for five vineyards of diverse age and management. The data was obtained as part of an experiment to improve fruit set and yield by applying combinations of gibberellin and 2-chloroethyltrimethyl ammonium chloride or 4-chlorophenoxyacetic acid. Four of the vineyards were located in the Brockman valley north of Perth, Western Australia, two of these were irrigated, one was rain fed and one received supplementary flood irrigation. The fifth lay in an adjacent area of coastal sand plain, at the foot of the Darling scarp, and was irrigated. The vines were aged from 6 to 50 years. Principal component analysis showed that vine age was negatively correlated with vigour (pruning weight) and with berry number per bunch. Vine age however was not strongly related to either yield or yield components (bunch number and berry volume). Sugar concentration was negatively correlated with all yield components but imprecisely modelled based on any combination of the measured variables. Berry number per vine appeared to be the underlying factor determining ,sink' strength though this was inextricably confounded with bunch number per vine. Interpretation of the data leads to the conclusion that increased berry volume is an inefficient means of increasing dried yield. This conclusion argues for caution in the application of plant growth regulators that act primarily to increase berry volume. Yield of sugar per vine was accurately modelled based on second order relationships with bunch number per vine, berry number per bunch, berry volume and pruning weight. Vine age also showed a second order relationship to yield although the range was relatively small. The observations are considered in terms of developing strategies for maximising dried yield and devising mathematical models to account for photoassimilate (dry matter) partitioning in Vitis. [source] Geometric morphometrics of corpus callosum and subcortical structures in the fetal-alcohol-affected brainBIRTH DEFECTS RESEARCH, Issue 1 2001Fred L. Bookstein Background Although experienced clinicians have been diagnosing fetal alcohol syndrome (FAS) for nearly 30 years, the rest of the spectrum of fetal alcohol damage is not being classified effectively. This article describes a quantification of neuroanatomical structure that may supply a useful discriminator of prenatal brain damage from alcohol. It is demonstrated in a data set of adults of both sexes. Methods Ninety adults (45 males) were examined by magnetic resonance imaging (MRI). These subjects were group-matched for age and ethnicity across three diagnoses: FAS, fetal alcohol effects (FAE), and normals. All FAS and FAE were heavily alcohol-exposed in utero; normals were not. From T1 -weighted MR brain images, we extracted 3D morphometric representations of shape for 33-landmark point configurations and 40-point outlines of the corpus callosum along its midline (a slightly nonplanar structure). Results There are striking differences between exposed and unexposed in the statistical distributions of these two shapes. The differences are better characterized by excess variance in the exposed group than by any change in average landmark or outline shape. For each sex, combining the callosal outline data with the landmark data leads to a powerful quadratic discriminator of exposed from unexposed. The discriminating features include the relationship of brain stem to diencephalon, and localized variabilities of callosal outline shape, but not diagnosis (FAS vs. FAE). Conclusions Statistical analysis of brain shape is a powerful new source of information relevant to fetal alcohol spectrum nosology and etiology. Patients with FAS and FAE do not differ in these brain shape features, but both differ from the unexposed. The aspects of brain shape that are especially variable may be entailed in the underlying neuroteratogenetic mechanisms. Teratology 64:4,32, 2001. © 2001 Wiley-Liss, Inc. [source] |