The component polypeptide chains of bovine insulin nucleate or inhibit aggregation of the parent protein in a conformation-dependent manner

Amyloid fibrils are typically rigid, unbrariched structures with diameters of similar to 10 nm and lengths up to several micrometres, and are associated with more than 20 diseases including Alzheimer's disease and type II diabetes. Insulin is a small, predominantly alpha-helical protein consisting of 51 residues in two disulfide-linked polypeptide chains that readily assembles into amyloid fibrils under conditions of low PH and elevated temperature. We demonstrate here that both the A-chain and the B-chain of insulin are capable of forming amyloid fibrils in isolation under similar conditions, with fibrillar morphologies that differ from those composed of intact insulin. Both the A-chain and B-chain fibrils were found to be able to cross-seed the fibrillization of the parent protein, although these reactions were substantially less efficient than self-seeding with fibrils composed of full-length insulin. In both cases, the cross-seeded fibrils were morphologically distinct from the seeding, material, but shared common characteristics with typical insulin fibrils, including a very similar helical repeat. The broader distribution of heights of the cross-seeded fibrils compared to typical insulin fibrils, however, indicates that their underling protofilament hierarchy may be subtly different. In addition, and remarkably in view of this seeding behavior, the soluble forms of the A-chain and B-chain peptides were found to be capable of inhibiting insulin fibril formation. Studies using mass spectrometry suggest that this behavior might be attributable to complex formation between insulin and the A-chain and B-chain peptides. The finding that the same chemical form of a polypeptide chain in different physical states can either stimulate or inhibit the conversion of a protein into amyloid fibrils sheds new light on the mechanisms underlying fibril formation, fibril strain propagation and amyloid disease initiation and progression. (c) 2006 Elsevier Ltd. All rights reserved.

Full-dimensional vibrational calculations for H5O2+ using an ab initio potential energy surface

We report quantum diffusion Monte Carlo (DMC) and variational calculations in full dimensionality for selected vibrational states of H5O2+ using a new ab initio potential energy surface [X. Huang, B. Braams, and J. M. Bowman, J. Chem. Phys. 122, 044308 (2005)]. The energy and properties of the zero-point state are focused on in the rigorous DMC calculations. OH-stretch fundamentals are also calculated using "fixed-node" DMC calculations and variationally using two versions of the code MULTIMODE. These results are compared with infrared multiphoton dissociation measurements of Yeh [L. I. Yeh, M. Okumura, J. D. Myers, J. M. Price, and Y. T. Lee, J. Chem. Phys. 91, 7319 (1989)]. Some preliminary results for the energies of several modes of the shared hydrogen are also reported.

Lighting the homes of people who are visually impaired

An extended research project, funded by the Thomas Pocklington Trust, and carried out by the Research Group for Inclusive Environments (RGIE) at The University of Reading, has examined the lighting found in the homes of people who are visually impaired (VIP). This paper will summarise the results of this substantive study. All the surveyed homes have been occupied by people with sight loss, some of the dwellings were shared with sighted partners. There are several safety issues concerning domestic lighting where inadequate provision may contribute to the incidence of personal injuries occurring in the home. Qualitative and quantitative data from questionnaires, photometric surveys and faceto- face interviews have been obtained from 57 homes. The nature and extent of the visual impairment of each study participant has been identified. This paper will identify important findings from the study, including: a range of areas and tasks within the home that visually impaired people find inadequately lit; the variability of illuminance provided for task lighting and general lighting; and how effective visually impaired people find a selection different lighting systems to those that they commonly use. The research team are able to offer preliminary design guidance for lighting the homes of people who are visually impaired. These will be summarised in the paper.

Beyond words: Aesthetic knowledge and knowing in design

Aesthetic knowledge comes from practitioners understanding the look, feel, smell, taste and sound of things. It is vital to work in many organizational contexts. In this paper, we explore aesthetic knowledge and knowing in organizations through detailed observation of design work in the architectural practice Edward Cullinan Architects. Through our research, we explore aesthetic knowledge in the context of architectural work, we unpack what it is, how it is generated, and how it is applied in design projects, shared between practitioners and developed at the level of the organization. Our analysis suggests that aesthetic knowledge plays an important part in organizational practice, not only as the symbolic context for work, but as an integral part of the work that people do. It suggests that aesthetic reflexivity, which involves an opening up and questioning of what is known, is experienced as part of practice as well as a `time out' from practice.

Knowledge sharing: Context, confusion and controversy

Project managers in the construction industry increasingly seek to learn from other industrial sectors. Knowledge sharing between different contexts is thus viewed as an essential source of competitive advantage. It is important therefore for project managers from all sectors to address and develop appropriate methods of knowledge sharing. However, too often it is assumed that knowledge freely exists and can be captured and shared between contexts. Such assumptions belie complexities and problems awaiting the unsuspecting knowledge-sharing protagonist. Knowledge per se is a problematic esoteric concept that does not lend itself easily to codification. Specifically tacit knowledge possessed by individuals, presents particular methodological issues for those considering harnessing its utility in return for competitive advantage. The notion that knowledge is also embedded in specific social contexts compounds this complexity. It is argued that knowledge is highly individualistic and concomitant with the various surrounding contexts within which it is shaped and enacted. Indeed, these contexts are also shaped as a consequence of knowledge adding further complexity to the problem domain. Current methods of knowledge capture, transfer and, sharing fall short of addressing these problematic issues. Research is presented that addresses these problems and proposes an alternative method of knowledge sharing. Drawing on data and observations collected from its application, the findings clearly demonstrate the crucial role of re-contextualisation, social interaction and dialectic debate in understanding knowledge sharing.

Learning across business sectors: Knowledge sharing between aerospace and construction

This report addresses the extent that managerial practices can be shared between the aerospace and construction sectors. Current recipes for learning from other industries tend to be oversimplistic and often fail to recognise the embedded and contextual nature of managerial knowledge. Knowledge sharing between business sectors is best understood as an essential source of innovation. The process of comparison challenges assumptions and better equips managers to cope with future change. Comparisons between the aerospace and construction sectors are especially useful because they are so different. The two sectors differ hugely in terms of their institutional context, structure and technological intensity. The aerospace sector has experienced extensive consolidation and is dominated by a small number of global companies. Aerospace companies operate within complex networks of global interdependency such that collaborative working is a commercial imperative. In contrast, the construction sector remains highly fragmented and is characterised by a continued reliance on small firms. The vast majority of construction firms compete within localised markets that are too often characterised by opportunistic behaviour. Comparing construction to aerospace highlights the unique characteristics of both sectors and helps explain how managerial practices are mediated by context. Detailed comparisons between the two sectors are made in a range of areas and guidance is provided for the implementation of knowledge sharing strategies within and across organisations. The commonly accepted notion of ‘best practice’ is exposed as a myth. Indeed, universal models of best practice can be detrimental to performance by deflecting from the need to adapt continuously to changing circumstances. Competitiveness in the construction sector too often rests on efficiency in managing contracts, with a particular emphasis on the allocation of risk. Innovation in construction tends to be problem-driven and is rarely shared from project to project. In aerospace, the dominant model of competitiveness means that firms have little choice other than to invest in continuous innovation, despite difficult trading conditions. Research and development (R&D) expenditure in aerospace continues to rise as a percentage of turnovers. A sustained capacity for innovation within the aerospace sector depends crucially upon stability and continuity of work. In the construction sector, the emergence of the ‘hollowed-out’ firm has undermined the industry’s capacity for innovation. Integrated procurement contexts such as prime contracting in construction potentially provide a more supportive climate for an innovation-based model of competitiveness. However, investment in new ways of working depends upon a shift in thinking not only amongst construction contractors, but also amongst the industry’s major clients.

Role of knowledge in managing construction change

Purpose-Unplanned changes in construction projects are common and lead to disruptive effects such as project delays, cost overruns and quality deviations. Rework due to unplanned changes can cost 10-15 per cent of contract value. By managing these changes more effectively, these disruptive effects can be minimised. Previous research has approached this problem from an information-processing view. In this knowledge age, the purpose of this paper is to argue that effective change management can be brought about by better understanding the significant role of knowledge during change situations. Design/methodology/approach - Within this knowledge-based context, the question of how construction project teams manage knowledge during unplanned change in the construction phase within collaborative team settings is investigated through a selected case study sample within the UK construction industry. Findings- Case study findings conclude that different forms of knowledge are created and shared between project team members during change events which is very much socially constructed and centred on tacit knowledge and experience of project personnel. Originality/value- Building on the case study findings the paper finally offers a model that represents the role of knowledge during managing project change.

The relationship between phonological awareness and word reading accuracy in Oriya and English: A Study of Oriya-speaking fifth-graders

This study investigated the relationships between phonological awareness and reading in Oriya and English. Oriya is the official language of Orissa, an eastern state of India. The writing system is an alphasyllabary. Ninety-nine fifth grade children (mean age 9 years 7 months) were assessed on measures of phonological awareness, word reading and pseudo-word reading in both languages. Forty-eight of the children attended Oriya-medium schools where they received literacy instruction in Oriya from grade 1 and learned English from grade 2. Fifty-one children attended English-medium schools where they received literacy instruction in English from grade 1 and in Oriya from grade 2. The results showed that phonological awareness in Oriya contributed significantly to reading Oriya and English words and pseudo-words for the children in the Oriya-medium schools. However, it only contributed to Oriya pseudo-word reading and English word reading for children in the English-medium schools. Phonological awareness in English contributed to English word and pseudo-word reading for both groups. Further analyses investigated the contribution of awareness of large phonological units (syllable, onsets and rimes) and small phonological units (phonemes) to reading in each language. The data suggest that cross-language transfer and facilitation of phonological awareness to word reading is not symmetrical across languages and may depend both on the characteristics of the different orthographies of the languages being learned and whether the first literacy language is also the first spoken language.

Literacy as a complex activity: deconstructing the simple view of reading

The Rose Review into the teaching of early reading recommended that the conceptual framework incorporated into the National Literacy Strategy Framework for Teaching – the Searchlights model of reading and its development – should be replaced by the Simple View of Reading. In this paper, we demonstrate how these two frameworks relate to each other, and show that nothing has been lost in this transformation from Searchlights to Simple View: on the contrary, much has been gained. That nothing has been lost is demonstrated by consideration of the underlying complexity inherent in each of the two dimensions delineated in the Simple View. That much has been gained is demonstrated by the increased understanding of each dimension that follows from careful scientific investigation of each. The better we understand what is involved in each dimension, the better placed we are to unravel and understand the essential, complex and continual interactions between each dimension which underlie skilled reading. This has clear implications for further improving the early teaching of reading.

Assessing reading at Key Stage 2: SATs as measures of children's inferential abilities

This article describes two studies. The first study was designed to investigate the ways in which the statutory assessments of reading for 11-year-old children in England assess inferential abilities. The second study was designed to investigate the levels of performance achieved in these tests in 2001 and 2002 by 11-year-old children attending state-funded local authority schools in one London borough. In the first study, content and questions used in the reading papers for the Standard Assessment Tasks (SATs) in the years 2001 and 2002 were analysed to see what types of inference were being assessed. This analysis suggested that the complexity involved in inference making and the variety of inference types that are made during the reading process are not adequately sampled in the SATs. Similar inadequacies are evident in the ways in which the programmes of study for literacy recommended by central government deal with inference. In the second study, scripts of completed SATs reading papers for 2001 and 2002 were analysed to investigate the levels of inferential ability evident in scripts of children achieving different SATs levels. The analysis in this article suggests that children who only just achieve the 'target' Level 4 do so with minimal use of inference skills. They are particularly weak in making inferences that require the application of background knowledge. Thus, many children who achieve the reading level (Level 4) expected of 11-year-olds are entering secondary education with insecure inference-making skills that have not been recognised.