Intra- and interspecies interactions between prion proteins and effects of mutations and polymorphisms

Recently, crystallization of the prion protein in a dimeric form was reported. Here we show that native soluble homogenous FLAG-tagged prion proteins from hamster, man and cattle expressed in the baculovirus system are predominantly dimeric. The PrP/PrP interaction was confirmed in Semliki Forest virus-RNA transfected BHK cells co-expressing FLAG- and oligohistidine-tagged human PrP. The yeast two-hybrid system identified the octarepeat region and the C-terminal structured domain (aa90-aa230) of PrP as PrP/PrP interaction domains. Additional octarepeats identified in patients suffering from fCJD reduced (wtPrP versus PrP+90R) and completely abolished (PrP+90R versus PrP+90R) the PrP/PrP interaction in the yeast two-hybrid system. In contrast, the Met/Val polymorphism (aa129), the GSS mutation Pro102Leu and the FFI mutation Asp178Asn did not affect PrP/PrP interactions. Proof of interactions between human or sheep and bovine PrP, and sheep and human PrP, as well as lack of interactions between human or bovine PrP and hamster PrP suggest that interspecies PrP interaction studies in the yeast two-hybrid system may serve as a rapid pre-assay to investigate species barriers in prion diseases

A terminal assessment of stages theory : introducing a dynamic states approach to entrepreneurship

Stages of Growth models were the most frequent theoretical approach to understanding entrepreneurial business growth from 1962 to 2006; they built on the growth imperative and developmental models of that time. An analysis of the universe of such models (N=104) published in the management literature shows no consensus on basic constructs of the approach, nor is there any empirical confirmations of stages theory. However, by changing two propositions of the stages models, a new dynamic states approach is derived. The dynamic states approach has far greater explanatory power than its precursor, and is compatible with leading edge research in entrepreneurship

Learning physics in context: a study of student learning about electricity and magnetism

This paper re-centres the discussion of student learning in physics to focus on context. In order to do so, a theoretically-motivated understanding of context is developed. Given a well-defined notion of context, data from a novel university class in electricity and magnetism are analyzed to demonstrate the central and inextricable role of context in student learning. This work sits within a broader effort to create and analyze environments which support student learning in the sciencesComment: 36 pages, 4 Figure

A multilevel neo-institutional analysis of infection prevention and control in English hospitals: coerced safety culture change?

Despite committed policy, regulative and professional efforts on healthcare safety, little is known about how such macro-interventions permeate organisations and shape culture over time. Informed by neo-institutional theory, we examined how inter-organisational influences shaped safety practices and inter-subjective meanings following efforts for coerced culture change. We traced macro-influences from 2000 to 2015 in infection prevention and control (IPC). Safety perceptions and meanings were inductively analysed from 130 in-depth qualitative interviews with senior- and middle-level managers from 30 English hospitals. A total of 869 institutional interventions were identified; 69% had a regulative component. In this context of forced implementation of safety practices, staff experienced inherent tensions concerning the scope of safety, their ability to be open and prioritisation of external mandates over local need. These tensions stemmed from conflicts among three co-existing institutional logics prevalent in the NHS. In response to requests for change, staff flexibly drew from a repertoire of cognitive, material and symbolic resources within and outside their organisations. They crafted 'strategies of action', guided by a situated assessment of first-hand practice experiences complementing collective evaluations of interventions such as 'pragmatic', 'sensible' and also 'legitimate'. Macro-institutional forces exerted influence either directly on individuals or indirectly by enriching the organisational cultural repertoire

Sustainable change: long-term efforts toward developing a learning organization

Globalization and intensified competition require organizations to change and adapt to dynamic environments in order to stay competitive. This article describes a longitudinal action research study supporting the strategic change of a trading company. The strategic change was accompanied by planned changes in organizational structures and processes, management systems, emerging changes in leadership, and organization members’ attitudes and behaviors, and it was supported by management development activities. Longitudinal data over a 4-year period including participant observation and interviews reveal that a systemic approach, a learning and becoming perspective toward change, trust, an appropriate role perception, and the specific use of management instruments contribute to sustained change that resulted in performance improvements and a move toward a learning organization. We conclude with implications for strategic change and suggestions for further research in this area

Machine Learning in Automated Text Categorization

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last ten years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert manpower, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

Social Network Analysis: Recent Achievements and Current Controversies

Network analysis has grown rapidly over the past two decades, but criticisms of the approach have increased as well This article focuses on several accomplishments and unresolved problems of the network approach In the first section. I illustrate the value of the network model in several substantive areas. focusing on studies of centrahty and power, network subgroups, and interorganizational relations I then discuss three issues over which the approach has provoked controversy the relation between network analysis and rational choice theory; the role of norms and culture, and the question of human agency I conclude with some examples of how network theorists are addressing these problemsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68023/2/10.1177_000169939403700403.pd