Markers of automaticity in sleep-associated consolidation of novel words

Two experiments investigated effects of sleep on consolidation and integration of novel form-meaning mappings using size congruity and semantic distance paradigms. Both paradigms have been used in previous studies to measure automatic access to word meanings. When participants compare semantic or physical font size of written word-pairs (e.g. BEE–COW), judgments are typically faster if relative sizes are congruent across both dimensions. Semantic distance effects are also found for wellestablished words, with semantic size judgements faster for pairs that differ substantially on this dimension. English-speaking participants learned novel form-meaning mappings with Mandarin (Experiment 1) or Malay (Experiment 2) words and were tested following overnight sleep or a similar duration awake. Judgements on English words controlled for circadian effects. The sleep group demonstrated selective stronger size congruity and semantic distance effects for novel word-pairs. This benefit occurred in Experiment 1 for semantic size comparisons of novel words, and in Experiment 2 on comparisons where novel pairs had large distances and font differences (for congruity effects) or in congruent trials (for semantic distance effects). Conversely, these effects were equivalent across sleep and wake for English words. Experiment 2 included polysomnography data and revealed that changes in the strength of semantic distance and congruity effects were positively correlated with slow-wave sleep and sleep spindles respectively. These findings support systems consolidation accounts of declarative learning and suggest that sleep plays an active role in integrating new words with existing knowledge, resulting in increased automatic access of the acquired knowledge

Flow of evaporating, gravity-driven thin liquid films over topography

The effect of topography on the free surface and solvent concentration profiles of an evaporating thin film of liquid flowing down an inclined plane is considered. The liquid is assumed to be composed of a resin dissolved in a volatile solvent with the associated solvent concentration equation derived on the basis of the well-mixed approximation. The dynamics of the film is formulated as a lubrication approximation and the effect of a composition-dependent viscosity is included in the model. The resulting time-dependent, nonlinear, coupled set of governing equations is solved using a full approximation storage multigrid method. The approach is first validated against a closed-form analytical solution for the case of a gravity-driven, evaporating thin film flowing down a flat substrate. Analysis of the results for a range of topography shapes reveal that although a full-width, spanwise topography such as a step-up or a step-down does not affect the composition of the film, the same is no longer true for the case of localized topography, such as a peak or a trough, for which clear nonuniformities of the solvent concentration profile can be observed in the wake of the topography

Variability of Active Galactic Nuclei from the Optical to X-ray Regions

Some progress in understanding AGN variability is reviewed. Reprocessing of X-ray radiation to produce significant amounts of longer-wavelength continua seems to be ruled out. In some objects where there has been correlated X-ray and optical variability, the amplitude of the optical variability has exceeded the amplitude of X-ray variability. We suggest that accelerated particles striking material could be linking X-ray and optical variability (as in activity in the solar chromosphere). Beaming effects could be significant in all types of AGN. The diversity in optical/X-ray relationships at different times in the same object, and between different objects, might be explained by changes in geometry and directions of motion relative to our line of sight. Linear shot-noise models of the variability are ruled out; instead there must be large-scale organization of variability. Variability occurs on light-crossing timescales rather than viscous timescales and this probably rules out the standard Shakura-Sunyaev accretion disk. Radio-loud and radio-quiet AGNs have similar continuum shapes and similar variability properties. This suggests similar continuum origins and variability mechanisms. Despite their extreme X-ray variability, narrow-line Seyfert 1s (NLS1s) do not show extreme optical variability.Comment: Invited talk given at Euro Asian Astronomical Society meeting in Moscow, June 2002. 20 pages, 4 figures. References update

A combined experimental and computational fluid dynamics analysis of the dynamics of drop formation

This article presents a complementary experimental and computational investigation of the effect of viscosity and flowrate on the dynamics of drop formation in the dripping mode. In contrast to previous studies, numerical simulations are performed with two popular commercial computational fluid dynamics (CFD) packages, CFX and FLOW-3D, both of which employ the volume of fluid (VOF) method. Comparison with previously published experimental and computational data and new experimental results reported here highlight the capabilities and limitations of the aforementioned packages

Eddy genesis and manipulation in plane laminar shear flow

Eddy formation and presence in a plane laminar shear flow configuration consisting of two infinitely long plates orientated parallel to each other is investigated theoretically. The upper plate, which is planar, drives the flow; the lower one has a sinusoidal profile and is fixed. The governing equations are solved via a full finite element formulation for the general case and semi-analytically at the Stokes flow limit. The effects of varying geometry (involving changes in the mean plate separation or the amplitude and wavelength of the lower plate) and inertia are explored separately. For Stokes flow and varying geometry, excellent agreement between the two methods of solution is found. Of particular interest with regard to the flow structure is the importance of the clearance that exists between the upper plate and the tops of the corrugations forming the lower one. When the clearance is large, an eddy is only present at sufficiently large amplitudes or small wavelengths. However, as the plate clearance is reduced, a critical value is found which triggers the formation of an eddy in an otherwise fully attached flow for any finite amplitude and arbitrarily large wavelength. This is a precursor to the primary eddy to be expected in the lid-driven cavity flow which is formed in the limit of zero clearance between the plates. The influence of the flow driving mechanism is assessed by comparison with corresponding solutions for the case of gravity-driven fluid films flowing over an undulating substrate. When inertia is present, the flow generally becomes asymmetrical. However, it is found that for large mean plate separations the flow local to the lower plate becomes effectively decoupled from the inertia dominated overlying flow if the wavelength of the lower plate is sufficiently small. In such cases the local flow retains its symmetry. A local Reynolds number based on the wavelength is shown to be useful in characterising these large-gap flows. As the mean plate separation is reduced, the form of the asymmetry caused by inertia changes, and becomes strongly dependent on the plate separation. For lower plate wavelengths which do not exhibit a cinematically induced secondary eddy, an inertially induced secondary eddy can be created if the mean plate separation is sufficiently small and the global Reynolds number sufficiently large

Unexpected benefits of pre-university skills training for A-level students

First-year undergraduates can find the transition from the prescriptive learning environment at school to one of self-directed learning at university, a considerable challenge. A Pre-university Skills Course (PSC) was developed to address this issue by preparing sixth formers for the university learning style. It was piloted with students in the year prior to A-level examinations at a selective state-funded school in East Anglia. The present paper examines the effect of the course on the students’ A-level tariff. Chi-squared analysis of A-level grades of students with comparable GCSE results, indicate that students who undertook the PSC performed significantly better in their A-level results than those who did not. These data demonstrate how skills training might improve A-level performance and assist in the transition to university

Dynamic wetting in metering and pre-metered roll coating

Ye

Development of a Spheroid Model to Investigate Drug-Induced Liver Injury

Drug induced liver injury is a major problem for the pharmaceutical industry and health services. Yet 30-40 % of human hepatotoxins go undetected during in vitro studies. Hence, more predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids show promise as a novel model to investigate drug-induced liver injury with preliminary studies indicating the ability of spheroids to detect hepatotoxins as well as displaying an enhanced functional lifespan compared to 2D monocultures. The aim of this thesis was to develop an improved in vitro model to investigate drug-induced liver injury. A viable C3A spheroid model with a lifespan of 32 days was successfully optimised. A characterisation of the spheroid model was performed, revealing direct cell-cell contacts, 3D morphology and cellular polarisation, hence recapitulating corresponding features of human liver tissue. Subsequently, liver-specific functions were investigated in the C3A spheroids and were found to display zonation, functional transporters, CYP enzyme activity, albumin production, urea synthesis and functional mitochondria. After validating the biology of the model, the ability of the spheroids to detect hepatotoxins was examined. The C3A spheroid model correctly identified 66.6 % of hepatotoxins to have a risk of liver injury, a higher predictive value than a 2D model. As hepatocytes only represent 60 % of the cells in the liver it was predicted that including non-parenchymal cells in the C3A spheroid model would cause increased sensitivity to hepatotoxins. Indeed when C3A spheroids were co-cultured with endothelial cells or immune cells they correctly predicted more compounds to have a risk of human hepatotoxicity, improving their predictivity to 91.6 % and 83.3 % respectively. It has been established that novel biomarkers of liver injury HMGB1, keratin 18 and miR-122 have enhanced sensitivity when compared to current clinical diagnostic markers, however they have not been extensively analysed in vitro. It was determined that keratin 18 could be quantified from the C3A spheroid model and provides important mechanistic insight into the mechanism of cell injury occurring. Mitochondrial damage is implicated in up to 50 % of human hepatotoxins. It was hypothesised that by analysing mitochondrial function in more detail one could reveal the mechanism of action by which a compound might be causing toxicity. Mitochondrial dysfunction could be successfully analysed in the C3A spheroids, which were found to be more sensitive to mitochondrial toxins than 2D cells. To conclude; C3A spheroids act as a human-relevant in vitro model with the potential to be incorporated into an initial drug safety screen, replacing 2D models with poor sensitivity and specificity. Results suggest that the inclusion of non-parenchymal cells may be advantageous to liver models. Furthermore the analysis of endpoints including clinical biomarkers and mitochondrial function may improve the sensitivity of the drug screen

Evidence for Structural Variants of a- and b-Type Peptide Fragment Ions Using Combined Ion Mobility/Mass Spectrometry

Tandem mass spectrometry (MS/MS) of peptides plays a key role in the field of proteomics, and an understanding of the fragmentation mechanisms involved is vital for data interpretation. Not all the fragment ions observed by low-energy collision-induced dissociation of protonated peptides are readily explained by the generally accepted structures for a- and b-ions. The possibility of a macrocyclic structure for b-type ions has been recently proposed. In this study, we have undertaken investigations of linear protonated YAGFL-NH2, N-acetylated-YAGFL-NH2, and cyclo-(YAGFL) peptides and their fragments using a combination of ion mobility (IM) separation and mass spectrometry. The use of IM in this work both gives insight into relative structural forms of the ion species and crucial separation of isobaric species. Our study provides compelling evidence for the formation of a stable macrocyclic structure for the b5 ion generated by fragmentation of protonated linear YAGFL-NH2. Additionally we demonstrate that the a4 ion fragment of protonated YAGFL-NH2 has at least two structures; one of which is attributable to a macrocyclic structure on the basis of its subsequent fragmentation. More generally, this work emphasizes the value of combined IM-MS/MS in probing the detailed fragmentation mechanisms of peptide ions, and illustrates the use of combined ion mobility/collisional activation/mass spectrometry analysis in achieving an effective enhancement of the resolution of the mobility separator