The prompt hypothesis: clarification requests as corrective input for grammatical errors

The potential of clarification questions (CQs) to act as a form of corrective input for young children's grammatical errors was examined. Corrective responses were operationalized as those occasions when child speech shifted from erroneous to correct (E -> C) contingent on a clarification question. It was predicted that E -> C sequences would prevail over shifts in the opposite direction (C -> E), as can occur in the case of nonerror-contingent CQs. This prediction was tested via a standard intervention paradigm, whereby every 60s a sequence of two clarification requests (either specific or general) was introduced into conversation with a total of 45 2- and 4-year-old children. For 10 categories of grammatical structure, E -> C sequences predominated over their C -> E counterparts, with levels of E -> C shifts increasing after two clarification questions. Children were also more reluctant to repeat erroneous forms than their correct counterparts, following the intervention of CQs. The findings provide support for Saxton's prompt hypothesis, which predicts that error-contingent CQs bear the potential to cue recall of previously acquired grammatical forms.

A refined quartic forcefield for acetylene: accurate calculation of the vibrational spectrum

It is now possible to calculate the nine-dimensional rovibrational wavefunctions of sequentially bonded four-atom molecules variationally without dynamical approximation. In the case of HCCH, the simplest such molecule, many hundreds of rovibrational (J = 0, 1, 2) levels can be converged to better than 1.5 cm −1. Variational calculations of this kind are used here systematically to refine the well-known quartic valence-coordinate forcefleld of Strey and Mills [J.Mol. Spectrosc.59, 103-115 (1976)] against experimental term values up to three C-H stretch quanta for the principal and two deuterated isotopomers, yielding a new surface that reproduces the energies of all the known Σ, Π, and Δ states of these species up to the energy of two C-H stretch quanta with an rms error of 3 cm−1 . The refined forcefield is used to study the resonances associated with the accidental degeneracies (ν2 + ν4 + ν5, ν3) and (ν2 + 2ν5, ν1) in the principal isotopomer, leading to a clarification of the assignment of she experimentally detected states in the 2ν3 and 3ν3, polyads, and to the finding that vibrational Coriolis (kinetic energy) terms, rather than quartic anharmonicities in the potential, are the primary cause of the resonant interactions. Using a new cubic ab initio electric dipole field to calculate IR absorption coefficients, 24 undetected Σ and Π states of 1H12C12C1H and 5 undetected Σ states of D12C12CD are identified as candidates for experimental study, and their calculated energies and assignments are given.

The role of Wnt signalling in the development of somites and neural crest

The Wnt family of secreted signalling molecules controls a wide range of developmental processes in all metazoans. In this investigation we concentrate on the role that members of this family play during the development of (1) the somites and (2) the neural crest. (3) We also isolate a novel component of the Wnt signalling pathway called Naked cuticle and investigate the role that this protein may play in both of the previously mentioned developmental processes. (1) In higher vertebrates the paraxial mesoderm undergoes a mesenchymal-to-epithelial transformation to form segmentally organised structures called somites. Experiments have shown that signals originating from the ectoderm overlying the somites or from midline structures are required for the formation of the somites, but their identity has yet to be determined. Wnt6 is a good candidate as a somite epithelialisation factor from the ectoderm since it is expressed in this tissue. In this study we show that injection of Wnt6-producing cells beneath the ectoderm at the level of the segmental plate or lateral to the segmental plate leads to the formation of numerous small epithelial somites. We show that Wnts are indeed responsible for the epithelialisation of somites by applying Wnt antagonists which result in the segmental plate being unable to form somites. These results show that Wnt6, the only member of this family to be localised to the chick paraxial ectoderm, is able to regulate the development of epithelial somites and that cellular organisation is pivotal in the execution of the differentiation programmes. (2) The neural crest is a population of multipotent progenitor cells that arise from the neural ectoderm in all vertebrate embryos and form a multitude of derivatives including the peripheral sensory neurons, the enteric nervous system, Schwann cells, pigment cells and parts of the craniofacial skeleton. The induction of the neural crest relies on an ectodermally derived signal, but the identity of the molecule performing this role in amniotes is not known. Here we show that Wnt6, a protein expressed in the ectoderm, induces neural crest production. (3) The intracellular response to Wnt signalling depends on the choice of signalling cascade activated in the responding cell. Cells can activate either the canonical pathway that modulates gene expression to control cellular differentiation and proliferation, or the non-canonical pathway that controls cell polarity and movement (Pandur et al. 2002b). Recent work has identified the protein Naked cuticle as an intracellular switch promoting the non-canonical pathway at the expense of the canonical pathway. We have cloned chick Naked cuticle-1 (cNkd1) and demonstrate that it is expressed in a dynamic manner during early embryogenesis. We show that it is expressed in the somites and in particular regions where cells are undergoing movement. Lastly our study shows that the expression of cNkd1 is regulated by Wnt expression originating from the neural tube. This study provides evidence that non-canonical Wnt signalling plays a part in somite development.

Total synthesis of (+/-) maculalactone A, maculalactone B and maculalactone C and the determination of the absolute configuration of natural (+) maculalactone A by asymmetric synthesis

Maculalactones A, B and C from the marine cyanobacterium Kyrtuthrix maculans are amongst the only compounds based on the tribenzylbutyrolactone skeleton known in nature and (+) maculalactone A from the natural source possesses significant biological activity against various marine herbivores and marine settlers. We now report a concise synthesis of racemic maculalactone A in five steps from inexpensive starting materials. Maculalactones B and C were synthesized by a minor modification to this procedure, and the synthetic design also permitted an asymmetric synthesis of maculalactone A to be achieved in around 85% ee. The (+) and (-) enantiomers of maculalactone A were assigned, respectively, to the S and R configurations on the basis of the chiral selectivity expected for catecholborane reduction of an unsymmetrical ketone in the presence of Corey's oxazoborolidine catalyst. Surprisingly, it appeared that natural (+) maculalactone A was biosynthesized in K. maculans in a partially racemic form, comprising ca. 90-95% of the (S) enantiomer and 5-10% of its (R) enantiomer. Coincidentally therefore, the percentage enantiomeric excess of the product obtained from asymmetric synthesis almost exactly matched that found in nature. (C) 2004 Elsevier Ltd. All rights reserved.

Enantiospecific assembly of a homochiral, hexanuclear palladium complex

The linking of orthopalladated ferrocenylene units by parabanato(2-) ligands results in enantiospecific assembly of a hexanuclear complex in which (i) the steric bulk of the ferrocenylene moiety, (ii) the folded configuration dictated by the imidato(2-) bridging ligand, and (iii) the strong preference for a trans arrangement of the carbonyl oxygen and ferrocenyl carbon atoms, combine to ensure that only ferrocenylene-palladium units with the same chirality can be located at adjacent positions in the assembled complex. The resulting tris-parabanato(2-)-bridged, hexapalladium complex is thus homochiral (R,R,R,R,R,R or S,S,S,S,S,S), as demonstrated by H-1 NMR spectroscopy and by X-ray analysis of a racemic crystal which shows the complex to possess a tapering, twisted, trigonal-prismatic skeleton of palladium atoms with threefold crystallographic symmetry. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

The effect of impaired thyroid function during development on the mechanical properties of avian bone

Thyroid hormones show fluctuating levels during the post-hatching development of birds. In this paper we report the results of the first mechanical tests to quantify the effect of hypothyroidism, during post-natal development, on the skeletal properties of a precocial bird, the barnacle goose, as determined by microhardness testing. The effect of hypothyroidism is tissue-specific; bone from the femora of birds is not significantly affected by induced hypothyroidism, however, there is a strong positive relationship between the levels of circulating thyroid hormones and the mechanical properties of bone from humeri. In the barnacle goose the development of the wing skeleton and musculature depends on an increase in circulating thyroid hormones and our analysis shows that, in its absence, the mechanical competence of the bone mineral itself is reduced in addition to the decreased bone length and muscle development previously reported in the literature. (C) 2004 Wiley-Liss, Inc.

The Nutritional Significance of Lipid Rafts

The structure, size, stability, and functionality of lipid rafts are still in debate, but recent techniques allowing direct visualization have characterized them in a wide range of cell types. Lipid rafts are potentially modifiable by diet, particularly (but not exclusively) by dietary fatty acids. However, it is not clear whether dietary polyunsaturated fatty acids (PUFAs) are incorporated into raft lipids or whether their low affinity to cholesterol disallows this and causes phase separation from rafts and displacement of raft proteins. This review examines the potential for dietary modification of raft structure and function in the immune system, brain and retinal tissue, the gut, and in cancer cells. Although there is increasing evidence to suggest that membrane microdomains, and their modulation, have an impact in health and disease, it is too early to judge whether modulation of lipid rafts is responsible for the immunomodulatory effects of n-3 PUFA. In addition to dietary fatty acids, gangliosides and cholesterol may also modulate microdomains in a number of tissues, and recent work has highlighted sphingolipids in membrane microdomains as potential targets for inhibition of tumor growth by n-3 PUFA. The roles of fatty acids and gangliosides in cognitive development, age-related cognitive decline, psychiatric disorders, and Alzheimer's disease are poorly understood and require clarification, particularly with respect to the contribution of lipid rafts. The roles of lipid rafts in cancer, in microbial pathogenesis, and in insulin resistance are only just emerging, but compelling evidence indicates the growing importance of membrane microdomains in health and disease.

Natural products as alternative treatments for metabolic bone disorders and for maintenance of bone health

Bone metabolism involves a complex balance between the deposition of matrix and mineralization and resorption. There is now good evidence that dietary components and herbal products can influence these processes, particularly by inhibiting bone resorption, thus having beneficial effects on the skeleton. For example, it has been reported that a number of common vegetables, including onion, garlic and parsley, can inhibit bone resorption in ovariectomized rats. Essential oils derived from sage, rosemary, thyme and other herbs inhibit osteoclast activity in vitro and in vitro and leading to an increase in bone mineral density. Soya, a rich source of isoflavones, has shown promising results and epidemiological evidence to support a use in maintaining bone health, and various traditional herbal formulae in Chinese and Ayurvedic medicine also have demonstrable effects in pharmacological models of osteoporosis. Recently, cannabinoids have been described as having positive effects on osteoblast differentiation, and the presence of cannabinoid receptors in bone tissue indicates a more complex role in bone metabolism than previously thought. The first part of this review briefly discusses normal bone metabolism and disorders caused by its disruption, with particular reference to osteoporosis and current pharmacological treatments. The effects of natural products on bone and connective tissue are then discussed, to include items of diet, herbal extracts and food supplements, with evidence for their efficacy outlined. Copyright (c) 2006 John Wiley & Sons, Ltd.

Childhood obesity: should primary school children be routinely screened? A systematic review and discussion of the evidence

Background: Population monitoring has been introduced in UK primary schools in an effort to track the growing obesity epidemic. It has been argued that parents should be informed of their child's results, but is there evidence that moving from monitoring to screening would be effective? We describe what is known about the effectiveness of monitoring and screening for overweight and obesity in primary school children and highlight areas where evidence is lacking and research should be prioritised. Design: Systematic review with discussion of evidence gaps and future research. Data sources: Published and unpublished studies ( any language) from electronic databases ( inception to July 2005), clinical experts, Primary Care Trusts and Strategic Health Authorities, and reference lists of retrieved studies. Review methods: We included any study that evaluated measures of overweight and obesity as part of a population-level assessment and excluded studies whose primary outcome measure was prevalence. Results: There were no trials assessing the effectiveness of monitoring or screening for overweight and obesity. Studies focussed on the diagnostic accuracy of measurements. Information on the attitudes of children, parents and health professionals to monitoring was extremely sparse. Conclusions: Our review found a lack of data on the potential impact of population monitoring or screening for obesity and more research is indicated. Identification of effective weight reduction strategies for children and clarification of the role of preventative measures are priorities. It is difficult to see how screening to identify individual children can be justified without effective interventions.

Social interaction deficits and conversational inadequacy in Williams syndrome

Research on social communication skills in individuals with Williams syndrome has been inconclusive, with some arguing that these skills are a relative strength and others that they are a weakness. The aim of the present study was to investigate social interaction abilities in a group of children with WS, and to compare them to a group of children with specific language impairment and a group of typically developing children. Semi-structured conversations were conducted and 100-150 utterances were selected for analysis in terms of exchange structure, turn taking, information transfer and conversational inadequacy. The statistical analyses showed that the children with WS had difficulties with exchange structure and responding appropriately to the interlocutor's requests for information and clarification. They also had significant difficulties with interpreting meaning and providing enough information for the conversational partner. Despite similar language abilities with a group of children with specific language impairment, the children with WS had different social interaction skills, which suggests that they follow an atypical trajectory of development and their neurolinguistic profile does not directly support innate modularity. (c) 2005 Elsevier Ltd. All rights reserved.

Association between feeding rate and parasitoid resistance in Drosophila melanogaster

Replicate lines of Drosophila melanogaster have been selected for increased resistance against one of two species of parasitoid wasp, Asobara tabida and Leptopilina boulardi. In both cases, it has been shown that an improved ability to mount an immunological defense against the parasitoid's egg is associated with reduced survival when the larvae are reared under conditions of low resource availability and thus high competition. We show here that in both sets of selected lines, lower competitive ability is associated with reduced rates of larval feeding, as measured by the frequency of retractions of the cephalopharyngeal skeleton. This suggests that the same or similar physiological processes are involved in the trade-off between competition and resistance against either parasitoid and shows how the interaction between adaptations for competition and natural enemy resistance may be mediated.

Comparison of methods for analysis of proteolysis by plasmin in milk

Sensitive methods that are currently used to monitor proteolysis by plasmin in milk are limited due to 7 their high cost and lack of standardisation for quality assurance in the various dairy laboratories. In 8 this study, four methods, trinitrobenzene sulphonic acid (TNBS), reverse phase high pressure liquid 9 chromatography (RP-HPLC), gel electrophoresis and fluorescamine, were selected to assess their 10 suitability for the detection of proteolysis in milk by plasmin. Commercial UHT milk was incubated 11 with plasmin at 37 °C for one week. Clarification was achieved by isoelectric precipitation (pH 4·6 12 soluble extracts)or 6% (final concentration) trichloroacetic acid (TCA). The pH 4·6 and 6% TCA 13 soluble extracts of milk showed high correlations (R2 > 0·93) by the TNBS, fluorescamine and 14 RP-HPLC methods, confirming increased proteolysis during storage. For gel electrophoresis,15 extensive proteolysis was confirmed by the disappearance of α- and β-casein bands on the seventh 16 day, which was more evident in the highest plasmin concentration. This was accompanied by the 17 appearance of α- and β-casein proteolysis products with higher intensities than on previous days, 18 implying that more products had been formed as a result of casein breakdown. The fluorescamine 19 method had a lower detection limit compared with the other methods, whereas gel electrophoresis 20 was the best qualitative method for monitoring β-casein proteolysis products. Although HPLC was the 21 most sensitive, the TNBS method is recommended for use in routine laboratory analysis on the basis 22 of its accuracy, reliability and simplicity.

Stochastic volatility jump-diffusions for European equity index dynamics

Major research on equity index dynamics has investigated only US indices (usually the S&P 500) and has provided contradictory results. In this paper a clarification and extension of that previous research is given. We find that European equity indices have quite different dynamics from the S&P 500. Each of the European indices considered may be satisfactorily modelled using either an affine model with price and volatility jumps or a GARCH volatility process without jumps. The S&P 500 dynamics are much more difficult to capture in a jump-diffusion framework.