No / Evidence suggests than human time perception is likely to reflect an ensemble of recent temporal experience. For example, prolonged exposure to consistent temporal patterns can adaptively realign the perception of event order, both within and between sensory modalities (e.g. Fujisaki et al., 2004 Nat. Neurosci., 7, 773-778). In addition, the observation that 'a watched pot never boils' serves to illustrate the fact that dynamic shifts in our attentional state can also produce marked distortions in our temporal estimates. In the current study we provide evidence for a hitherto unknown link between adaptation, temporal perception and our attentional state. We show that our ability to use recent sensory history as a perceptual baseline for ongoing temporal judgments is subject to striking top-down modulation via shifts in the observer's selective attention. Specifically, attending to the temporal structure of asynchronous auditory and visual adapting stimuli generates a substantial increase in the temporal recalibration induced by these stimuli. We propose a conceptual framework accounting for our findings whereby attention modulates the perceived salience of temporal patterns. This heightened salience allows the formation of audiovisual perceptual 'objects', defined solely by their temporal structure. Repeated exposure to these objects induces high-level pattern adaptation effects, akin to those found in visual and auditory domains (e.g. Leopold & Bondar (2005) Fitting the Mind to the World: Adaptation and Aftereffects in High-Level Vision. Oxford University Press, Oxford, 189-211; Schweinberger et al. (2008) Curr. Biol., 18, 684-688).

No / Activation of fibroblast growth factor receptors (FGFR) is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference (RNAi) genetic screens, we show that the EGF receptor (EGFR) limits sensitivity to FGFR inhibition in FGFR3-mutant and -translocated cell lines, but not in other FGFR-driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3-dependent lines, inhibition of FGFR3 results in transient downregulation of mitogen-activated protein kinase signaling that is rescued by rapid upregulation of EGFR signaling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signaling via repression of FGFR3, with EGFR inhibition rescued by delayed upregulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNAi screens in identifying common resistance mechanisms to targeted therapies. SIGNIFICANCE: Our data identify a novel therapeutic approach to the treatment of FGFR3-mutant cancer, emphasizing the potential of combination approaches targeting both FGFR3 and EGFR. Our data extend the role of EGFR in mediating resistance to inhibitors targeting a mutant oncogene, showing that EGFR signaling can repress mutant FGFR3 to induce intrinsic resistance to FGFR targeting.

No / Gas chromatography (GC), GC-mass spectrometry (GC-MS) and GC-combustion-isotope ratio MS (GC-C-IRMS) analyses of absorbed and surface lipid residues preserved in potsherds were used to explore the extent of pig product processing exploitation in the later British Neolithic Grooved Ware tradition. Assessments were made regarding whether porcine lipids were associated with specific Grooved Ware traits, i.e. decoration, substyle, geographical area and type of site. Two hundred and twenty-two Grooved Ware potsherds were analysed, 70% of which contained lipid concentrations considered significant (>5 μg g−1). All the lipid residues were dominated by animal fats, although plant and beeswax were also detected in a small number of extracts. δ13C values of the major fatty acid components of degraded animal fats (C16:0 and C18:0) were determined for 126 extracts and used to assign ruminant or porcine origins to the residues; 16% of these were found to have a predominantly porcine isotope signature. Statistical associations with pig exploitation were shown to exist with substyle, geographical area and site type, whereas, no relationship was seen between decoration and the type of commodity processed. Intact triacylglycerols were preserved in 19% of the sherds; half of these had distributions consistent with the identifications based on δ13C values, the remainder differed either due to the presence of mixed commodities or because lower molecular weight homologues had been lost due to degradation. In addition to the detection of pig exploitation, results from lipid residue analysis showed a good correlation with faunal assemblages, suggesting that stable isotope analysis may be used as a proxy for animal exploitation at sites where bones have not survived.

No / Six new multi-component crystals between 4-phenylpyridine and substituted benzoic acids (3-nitrobenzoic acid, 3,5-dinitrobenzoic acid, gallic acid, 4-aminobenozic acid, salicylic acid and 2-aminobenzoic acid) were created and characterized crystallographically to investigate the influence of chemical and structural factors on the hydrogen location between the two components. While the expected intermolecular interactions are formed between the acid and pyridine group in most cases, the gallic acid structure is anomalous forming an unexpected salt with pyridine to hydroxyl interactions. Calculations of the hydrogen bonding motifs indicate that the level of proton transfer (e.g. salt versus co-crystal formation) is not solely a function of the dimer geometry but influenced by the local crystallographic environment. Analysis of the crystal structures indicates the strength of the hydrogen bonding into this motif alters the expected protonation state from chemical considerations.

No / PURPOSE: To explore the use of crystal inter-planar d-spacings and slip-plane interaction energies for predicting and characterising mechanical properties of crystalline solids. METHODS: Potential relationships were evaluated between mechanical properties and inter-planar d-spacing, inter-planar interaction energy, and dispersive surface energy as determined using inverse gas chromatography (IGC) for a set of pharmaceutical materials. Inter-planar interaction energies were determined by molecular modelling. RESULTS: General trends were observed between mechanical properties and the largest inter-planar d-spacing, inter-planar interaction energies, and IGC dispersive surface energy. A number of materials showed significant deviations from general trends. Weak correlations and outliers were rationalised. CONCLUSIONS: Results suggest that the highest d-spacing of a material could serve as a first-order indicator for ranking mechanical behaviour of pharmaceutical powders, but with some reservation. Inter-planar interaction energy normalised for surface area shows only a weak link with mechanical properties and does not appear to capture essential physics of deformation. A novel framework linking mechanical properties of crystals to the distinct quantities, slip-plane energy barrier and inter-planar interaction (detachment) energy is proposed.

No / We report on the development and on the first use of the widefield surface plasmon (WSPR) microscope in the examination of the cell surface interface at submicron lateral resolutions. The microscope is Kohler illuminated and uses either a 1.45 numerical aperture (NA) oil immersion lens, or a 1.65 NA oil immersion lens to excite surface plasmons at the interface between a thin gold layer and a glass or sapphire cover slip. Like all surface plasmon microscope systems the WSPR has been proven in previous studies to also be capable of nanometric z-scale resolutions. In this study we used the system to image the interface between HaCaT cells and the gold layer. Imaging was performed in air using fixed samples and the 1.45 NA objective based system and also using live cells in culture media using the 1.65 NA based system. Imaging in air enabled the visualisation of high resolution and high-contrast submicron features identified by vinculin immunostaining as component of focal contacts and focal adhesions. In comparison, imaging in fluid enabled cell surface interfacial interactions to be tracked by time-lapse video WSPR microscopy. Our results indicate that the cell surface interface and thus cell signalling mechanisms may be readily interrogated in live cells without the use of labelling techniques.

No / Oxidative coupling of methane (OCM) is suggested to be a promising process for the conversion of the abundant natural gas into useful chemicals. However, this reaction faces many drawbacks such as low yields for higher hydrocarbons, fast catalyst deactivation, and huge heat effects of the reaction. Only a well-designed fluidized bed reactor is able to overcome effectively those disadvantages and to provide a satisfactory continuous operation. However, design approaches for fluidized bed reactors are still based on models developed during 70s and 80s, which cannot take into account various hydrodynamic effects on the reactor performance. Thus, a reactor designer has usually to rely on extensive experiments in order to improve the classical fluidized bed reactor design. In this work, the relevance of hydrodynamics, reactor geometry, and feeding policy on the performance of a fluidized bed reactor for the OCM is shown. For this purpose, several case studies of fluidized bed reactors are simulated in full 3D geometry under the same reaction conditions, but with different reactor geometries and feeding policy. These studies show the significance of hydrodynamic parameters for the reactor performance, and moreover, how fluidized bed reactor performance can be improved by a careful study of coupled momentum-mass transport-reaction phenomena. Furthermore, it can be demonstrated that a suitable distributed feeding policy of oxygen provides an improved yield while a traditional fluidized bed reactor design results in an inferior performance among all investigated cases.

No

No

No / BACKGROUND: Tripping is a common factor in falls and a typical safety strategy to avoid tripping on steps or stairs is to increase foot clearance over the step edge. In the present study we asked whether the perceived height of a step could be increased using a visual illusion and whether this would lead to the adoption of a safer stepping strategy, in terms of greater foot clearance over the step edge. The study also addressed the controversial question of whether motor actions are dissociated from visual perception. METHODOLOGY/PRINCIPAL FINDINGS: 21 young, healthy subjects perceived the step to be higher in a configuration of the horizontal-vertical illusion compared to a reverse configuration (p = 0.01). During a simple stepping task, maximum toe elevation changed by an amount corresponding to the size of the visual illusion (p<0.001). Linear regression analyses showed highly significant associations between perceived step height and maximum toe elevation for all conditions. CONCLUSIONS/SIGNIFICANCE: The perceived height of a step can be manipulated using a simple visual illusion, leading to the adoption of a safer stepping strategy in terms of greater foot clearance over a step edge. In addition, the strong link found between perception of a visual illusion and visuomotor action provides additional support to the view that the original, controversial proposal by Goodale and Milner (1992) of two separate and distinct visual streams for perception and visuomotor action should be re-evaluated.