No / In visual search experiments, the subject looks for a target item in a display containing different distractor items. The reaction time (RT) to find the target is measured as a function of the number of distractors (set size). RT is either constant, or increases linearly, with set size. Here we suggest a two-stage model for search in which items are first selected and then recognized. The selection process is modeled by (a) grouping items into a hierarchical cluster tree, in which each cluster node contains a list of all the features of items in the cluster, called the object file, and (b) recursively searching the tree by comparing target features to the cluster object file to quickly determine whether the cluster could contain the target. This model is able to account for both constant and linear RT versus set size functions. In addition, it provides a simple and accurate account of conjunction searches (e.g., looking for a red N among red Os and green Ns), in particular the variation in search rate as the distractor ratio is varied.

No / To obtain accurate results in the RHX dating of ceramics, it is essential that the RHX measurements are continued until the rate of mass gain is constant with (time)1/4. In this paper, we discuss how the initial stages of mass gain are affected by the specific surface area (SSA) of the ceramic material. The paper provides guidance on experimental protocols to avoid dating results being distorted by relatively early-time mass gain data.

Yes / The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide.

No / Tissue stem cells and germ line or embryonic stem cells were shown to have reduced oxidative metabolism, which was proposed to be an adaptive mechanism to reduce damage accumulation caused by reactive oxygen species. However, an alternate explanation is that stem cells are less dependent on specialized cytoplasmic functions compared with differentiated cells, therefore, having a high nuclear-to-cytoplasmic volume ratio and consequently a low mitochondrial content. To determine whether stem cells rely or not on mitochondrial respiration, we selectively ablated the electron transport chain in the basal layer of the epidermis, which includes the epidermal progenitor/stem cells (EPSCs). This was achieved using a loxP-flanked mitochondrial transcription factor A (Tfam) allele in conjunction with a keratin 14 Cre transgene. The epidermis of these animals (TfamEKO) showed a profound depletion of mitochondrial DNA and complete absence of respiratory chain complexes. However, despite a short lifespan due to malnutrition, epidermal development and skin barrier function were not impaired. Differentiation of epidermal layers was normal and no proliferation defect or major increase of apoptosis could be observed. In contrast, mice with an epidermal ablation of prohibitin-2, a scaffold protein in the inner mitochondrial membrane, displayed a dramatic phenotype observable already in utero, with severely impaired skin architecture and barrier function, ultimately causing death from dehydration shortly after birth. In conclusion, we here provide unequivocal evidence that EPSCs, and probably tissue stem cells in general, are independent of the mitochondrial respiratory chain, but still require a functional dynamic mitochondrial compartment.

Yes / Polysialic acid (polySia), an α-2,8-glycosidically linked polymer of sialic acid, is a developmentally regulated posttranslational modification predominantly found on NCAM (neuronal cell adhesion molecule). Whilst high levels are expressed during development, peripheral adult organs do not express polySia-NCAM. However, tumours of neural crest-origin re-express polySia-NCAM: its occurrence correlates with aggressive and invasive disease and poor clinical prognosis in different cancer types, notably including small cell lung cancer (SCLC), pancreatic cancer and neuroblastoma. In neuronal development, polySia-NCAM biosynthesis is catalysed by two polysialyltransferases, ST8SiaII and ST8SiaIV, but it is ST8SiaII that is the prominent enzyme in tumours. The aim of this study was to determine the effect of ST8SiaII inhibition by a small molecule on tumour cell migration, utilising cytidine monophosphate (CMP) as a tool compound. Using immunoblotting we showed that CMP reduced ST8iaII-mediated polysialylation of NCAM. Utilizing a novel HPLC-based assay to quantify polysialylation of a fluorescent acceptor (DMB-DP3), we demonstrated that CMP is a competitive inhibitor of ST8SiaII (Ki = 10 μM). Importantly, we have shown that CMP causes a concentration-dependent reduction in tumour cell-surface polySia expression, with an absence of toxicity. When ST8SiaII-expressing tumour cells (SH-SY5Y and C6-STX) were evaluated in 2D cell migration assays, ST8SiaII inhibition led to significant reductions in migration, while CMP had no effect on cells not expressing ST8SiaII (DLD-1 and C6-WT). The study demonstrates for the first time that a polysialyltransferase inhibitor can modulate migration in ST8SiaII-expressing tumour cells. We conclude that ST8SiaII can be considered a druggable target with the potential for interfering with a critical mechanism in tumour cell dissemination in metastatic cancers. / Yorkshire Cancer Research; EPSRC; Association for International Cancer Research; Jordanian Government PhD scholarship

No / We present a series of iterative methods to examine the problems associated with summed probability functions (SPFs) based on archaeological radiocarbon data. As a case study we use an SPF generated from a substantial radiocarbon data-set from the Irish Later Bronze and Iron Ages. We use simple numerical methods to show that real patterns can be deciphered from SPFs that can be used to trace and evaluate patterns of change. However, our results suggest that SPFs should not be used as a simple index of past human activity. / This research forms part of the project ‘Mobility, Climate and Culture: Re-modelling the Irish Iron Age’, funded by the British Academy through their BARDA scheme. Preliminary data collection was conducted as part of a pilot project funded by the Heritage Council of Ireland.

Yes / Purpose. A recent study suggested that updated spectacles could increase falls rate in older people. We hypothesized that this may be due to changes in spectacle magnification and this study assessed the effects of spectacle magnification on adaptive gait. Methods. Adaptive gait and visual function was measured in 10 older adults (mean age 77.1 ¿ 4.3 years) with the participants¿ optimal refractive correction and when blurred with +1.00DS, +2.00DS, -1.00DS and -2.00DS lenses. Adaptive gait measurements for the lead and trail foot included foot position before the step, toe clearance of the step edge and foot position on the step. Vision measurements included visual acuity, contrast sensitivity and stereoacuity. Results. The blur lenses led to equal decrements in visual acuity and stereoacuity for the +1.00DS and -1.00DS and the +2.00DS and -2.00DS lenses. However, they had very different effects on adaptive gait compared to the optimal correction: Positive blur lenses led to an increased distance of the feet from the step, increased vertical toe clearance and reduced distance of the lead heel position on the step. Negative lenses led to the opposite of these changes. Conclusion. The adaptive gait changes did not mirror the effects of blur on vision, but were driven by the magnification changes of the lenses. Steps appear closer and larger with positive lenses and further away and smaller with negative ones. Magnification likely explains the mobility problems some older adults have with updated spectacles and after cataract surgery. / Federation of Ophthalmic and Dispensing Opticians

No / This communication reports a novel solvent free method to generate and stabilise the triclinic form of artemisinin. We show that the stability of the triclinic form obtained by high temperature extrusion is greater than that of material made using a solvent based technique.

No / Crystallization of an isotactic polypropylene (iPP) homopolymer and two propylene/ethylene random copolymers (RACO), induced by high-stress shear, was studied using in situ synchrotron wide-angle X-ray diffraction (WAXD) at 137 °C. The “depth sectioning” method (Fernandez-Ballester Journal of Rheology 2009, 53 (5), 1229−1254) was applied in order to isolate the contributions of different layers in the stress gradient direction and to relate specific structural evolution to the corresponding local stress. This approach gives quantitative results in terms of the specific length of fibrillar nuclei as a function of the applied stress. As expected, crystallization becomes faster with increasing stress—from the inner to the outer layer—for all three materials. Stress-induced crystallization in a RACO with 7.3 mol % ethylene content was triggered at only 1 °C below its nominal melting temperature. The comparison of iPP and RACO’s with 3.4 and 7.3 mol % ethylene monomer reveals the effect of ethylene defects on high-stress shear induced crystallization at 137 °C. It is found that, for a given applied stress, the specific nuclei length formed by flow increases with ethylene content—which is attributed to a greater high molecular weight tail. However, the linear growth rate is significantly reduced by the presence of ethylene comonomers and it is found that this effect dominates the overall crystallization kinetics. Finally, a time lag is found between development of parent lamellae and the emergence of daughter lamellae, consistent with the concept of daughter lamellae nucleated by homoepitaxy on the lateral faces of existing parent lamellae.

No / The finite element simulation of a selection of two- and three-dimensional flow problems is presented, based upon the use of four different constitutive models for polymer melts (Oldroyd-B, Rolie-Poly, Pom-Pom and XPP). The mathematical and computational models are first introduced, before their application to a range of visco-elastic flows is described. Results demonstrate that the finite element models used here are able to re-produce predictions made by other published numerical simulations and, significantly, by carefully conducted physical experiments using a commercial-grade polystyrene melt in a three-dimensional contraction geometry. The paper also presents a systematic comparison and evaluation of the differences between two- and three-dimensional simulations of two different flow regimes: flow of an Oldroyd-B fluid around a cylinder and flow of a Rolie-Poly fluid into the contraction geometry. This comparison allows new observations to be made concerning the relatively poor quality of two-dimensional simulations for flows in even quite deep channels.