Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells

Type 2 hereditary hemochromatosis (HH) or juvenile hemochromatosis is an early onset, genetically heterogeneous, autosomal recessive disorder of iron overload. Type 2A HH is caused by mutations in the recently cloned hemojuvelin gene (HJV; also called HFE2) (Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L., Franchini, P. L., Dube, M. P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., Nemeth, E., Thompson, J., Risler, J. K., Zaborowska, C., Babakaiff, R., Radomski, C. C., Pape, T. D., Davidas, O., Christakis, J., Brissot, P., Lockitch, G., Ganz, T., Hayden, M. R., and Goldberg, Y. P. (2004) Nat. Genet. 36, 77–82), whereas Type 2B HH is caused by mutations in hepcidin. HJV is highly expressed in both skeletal muscle and liver. Mutations in HJV are implicated in the majority of diagnosed juvenile hemochromatosis patients. In this study, we stably transfected HJV cDNA into human embryonic kidney 293 cells and characterized the processing of HJV and its effect on iron homeostasis. Our results indicate that HJV is a glycosylphosphatidylinositol-linked protein and undergoes a partial autocatalytic cleavage during its intracellular processing. HJV co-immunoprecipitated with neogenin, a receptor involved in a variety of cellular signaling processes. It did not interact with the closely related receptor DCC (deleted in Colon Cancer). In addition, the HJV G320V mutant implicated in Type 2A HH did not co-immunoprecipitate with neogenin. Immunoblot analysis of ferritin levels and transferrin-55Fe accumulation studies indicated that the HJV-induced increase in intracellular iron levels in human embryonic kidney 293 cells is dependent on the presence of neogenin in the cells, thus linking these two proteins to intracellular iron homeostasis

Composite Fermion Wavefunctions Derived by Conformal Field Theory

The Jain theory of hierarchical Hall states is reconsidered in the light of recent analyses that have found exact relations between projected Jain wavefunctions and conformal field theory correlators. We show that the underlying conformal theory is precisely given by the W-infinity minimal models introduced earlier. This theory involves a reduction of the multicomponent Abelian theory that is similar to the projection to the lowest Landau level in the Jain approach. The projection yields quasihole excitations obeying non-Abelian fractional statistics. The analysis closely parallels the bosonic conformal theory description of the Pfaffian and Read-Rezayi states.Comment: 4 pages, 1 figur

Ontologies relevant to behaviour change interventions: a method for their development [version 2; peer review: 1 not approved]

Background: Behaviour and behaviour change are integral to many aspects of wellbeing and sustainability. However, reporting behaviour change interventions accurately and synthesising evidence about effective interventions is hindered by lacking a shared, scientific terminology to describe intervention characteristics. Ontologies are knowledge structures that provide controlled vocabularies to help unify and connect scientific fields. To date, there is no published guidance on the specific methods required to develop ontologies relevant to behaviour change. We report the creation and refinement of a method for developing ontologies that make up the Behaviour Change Intervention Ontology (BCIO). / Aims: (1) To describe the development method of the BCIO and explain its rationale; (2) To provide guidance on implementing the activities within the development method. / Method and results: The method for developing ontologies relevant to behaviour change interventions was constructed by considering principles of good practice in ontology development and identifying key activities required to follow those principles. The method’s details were refined through application to developing two ontologies. The resulting ontology development method involved: (1) defining the ontology’s scope; (2) identifying key entities; (3) refining the ontology through an iterative process of literature annotation, discussion and revision; (4) expert stakeholder review; (5) testing inter-rater reliability; (6) specifying relationships between entities, and; (7) disseminating and maintaining the ontology. Guidance is provided for conducting relevant activities for each step. / Conclusions: We have developed a detailed method for creating ontologies relevant to behaviour change interventions, together with practical guidance for each step, reflecting principles of good practice in ontology development. The most novel aspects of the method are the use of formal mechanisms for literature annotation and expert stakeholder review to develop and improve the ontology content. We suggest the mnemonic SELAR3, representing the method’s first six steps as Scope, Entities, Literature Annotation, Review, Reliability, Relationships

Representation of behaviour change interventions and their evaluation: Development of the Upper Level of the Behaviour Change Intervention Ontology [version 2; peer review: 1 approved, 1 approved with reservations]

Background: Behaviour change interventions (BCI), their contexts and evaluation methods are heterogeneous, making it difficult to synthesise evidence and make recommendations for real-world policy and practice. Ontologies provide a means for addressing this. They represent knowledge formally as entities and relationships using a common language able to cross disciplinary boundaries and topic domains. This paper reports the development of the upper level of the Behaviour Change Intervention Ontology (BCIO), which provides a systematic way to characterise BCIs, their contexts and their evaluations. Methods: Development took place in four steps. (1) Entities and relationships were identified by behavioural and social science experts, based on their knowledge of evidence and theory, and their practical experience of behaviour change interventions and evaluations. (2) The outputs of the first step were critically examined by a wider group of experts, including the study ontology expert and those experienced in annotating relevant literature using the initial ontology entities. The outputs of the second step were tested by (3) feedback from three external international experts in ontologies and (4) application of the prototype upper-level BCIO to annotating published reports; this informed the final development of the upper-level BCIO. Results: The final upper-level BCIO specifies 42 entities, including the BCI scenario, elaborated across 21 entities and 7 relationship types, and the BCI evaluation study comprising 10 entities and 9 relationship types. BCI scenario entities include the behaviour change intervention (content and delivery), outcome behaviour, mechanism of action, and its context, which includes population and setting. These entities have corresponding entities relating to the planning and reporting of interventions and their evaluations. Conclusions: The upper level of the BCIO provides a comprehensive and systematic framework for representing BCIs, their contexts and their evaluations. Keyword

Delivering Behaviour Change Interventions: Development of a Mode of Delivery Ontology [version 1; peer review: 1 approved, 1 approved with reservations]

Background: Investigating and improving the effects of behaviour change interventions requires detailed and consistent specification of all aspects of interventions. An important feature of interventions is the way in which these are delivered, i.e. their mode of delivery. This paper describes an ontology for specifying the mode of delivery of interventions, which forms part of the Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. / Methods: The Mode of Delivery Ontology was developed in an iterative process of annotating behaviour change interventions evaluation reports, and consulting with expert stakeholders. It consisted of seven steps: 1) annotation of 110 intervention reports to develop a preliminary classification of modes of delivery; 2) open review from international experts (n=25); 3) second round of annotations with 55 reports to test inter-rater reliability and identify limitations; 4) second round of expert review feedback (n=16); 5) final round of testing of the refined ontology by two annotators familiar and two annotators unfamiliar with the ontology; 6) specification of ontological relationships between entities; and 7) transformation into a machine-readable format using the Web Ontology Language (OWL) language and publishing online. / Results: The resulting ontology is a four-level hierarchical structure comprising 65 unique modes of delivery, organised by 15 upper-level classes: Informational, Environmental change, Somatic, Somatic alteration, Individual-based/ Pair-based /Group-based, Uni-directional/Interactional, Synchronous/ Asynchronous, Push/ Pull, Gamification, Arts feature. Relationships between entities consist of is_a. Inter-rater reliability of the Mode of Delivery Ontology for annotating intervention evaluation reports was a=0.80 (very good) for those familiar with the ontology and a= 0.58 (acceptable) for those unfamiliar with it. / Conclusion: The ontology can be used for both annotating and writing behaviour change intervention evaluation reports in a consistent and coherent manner, thereby improving evidence comparison, synthesis, replication, and implementation of effective interventions

Delivering Behaviour Change Interventions: Development of a Mode of Delivery Ontology [version 2; peer review: 2 approved]

Background: Investigating and improving the effects of behaviour change interventions requires detailed and consistent specification of all aspects of interventions. An important feature of interventions is the way in which these are delivered, i.e. their mode of delivery. This paper describes an ontology for specifying the mode of delivery of interventions, which forms part of the Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. Methods: The Mode of Delivery Ontology was developed in an iterative process of annotating behaviour change interventions evaluation reports, and consulting with expert stakeholders. It consisted of seven steps: 1) annotation of 110 intervention reports to develop a preliminary classification of modes of delivery; 2) open review from international experts (n=25); 3) second round of annotations with 55 reports to test inter-rater reliability and identify limitations; 4) second round of expert review feedback (n=16); 5) final round of testing of the refined ontology by two annotators familiar and two annotators unfamiliar with the ontology; 6) specification of ontological relationships between entities; and 7) transformation into a machine-readable format using the Web Ontology Language (OWL) and publishing online. Results: The resulting ontology is a four-level hierarchical structure comprising 65 unique modes of delivery, organised by 15 upper-level classes: Informational, Environmental change, Somatic, Somatic alteration, Individual-based/ Pair-based /Group-based, Uni-directional/Interactional, Synchronous/ Asynchronous, Push/ Pull, Gamification, Arts feature. Relationships between entities consist of is_a. Inter-rater reliability of the Mode of Delivery Ontology for annotating intervention evaluation reports was a=0.80 (very good) for those familiar with the ontology and a= 0.58 (acceptable) for those unfamiliar with it. Conclusion: The ontology can be used for both annotating and writing behaviour change intervention evaluation reports in a consistent and coherent manner, thereby improving evidence comparison, synthesis, replication, and implementation of effective interventions

Theory of the "honeycomb chain-channel" reconstruction of Si(111)3x1

First-principles electronic-structure methods are used to study a structural model for Ag/Si(111)3x1 recently proposed on the basis of transmission electron diffraction data. The fully relaxed geometry for this model is far more energetically favorable than any previously proposed, partly due to the unusual formation of a Si double bond in the surface layer. The calculated electronic properties of this model are in complete agreement with data from angle-resolved photoemission and scanning tunneling microscopy.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Lett (the ugly postscript error on page 4 has now been repaired

Development of an Intervention Setting Ontology for behaviour change: Specifying where interventions take place

Background: Contextual factors such as an intervention's setting are key to understanding how interventions to change behaviour have their effects and patterns of generalisation across contexts. The intervention's setting is not consistently reported in published reports of evaluations. Using ontologies to specify and classify intervention setting characteristics enables clear and reproducible reporting, thus aiding replication, implementation and evidence synthesis. This paper reports the development of a Setting Ontology for behaviour change interventions as part of a Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. Methods: The Intervention Setting Ontology was developed following methods for ontology development used in the Human Behaviour-Change Project: 1) Defining the ontology's scope, 2) Identifying key entities by reviewing existing classification systems (top-down) and 100 published behaviour change intervention reports (bottom-up), 3) Refining the preliminary ontology by literature annotation of 100 reports, 4) Stakeholder reviewing by 23 behavioural science and public health experts to refine the ontology, 5) Assessing inter-rater reliability of using the ontology by two annotators familiar with the ontology and two annotators unfamiliar with it, 6) Specifying ontological relationships between setting entities and 7) Making the Intervention Setting Ontology machine-readable using Web Ontology Language (OWL) and publishing online. Results: The Intervention Setting Ontology consists of 72 entities structured hierarchically with two upper-level classes: Physical setting including Geographic location, Attribute of location (including Area social and economic condition, Population and resource density sub-levels) and Intervention site (including Facility, Transportation and Outdoor environment sub-levels), as well as Social setting. Inter-rater reliability was found to be 0.73 (good) for those familiar with the ontology and 0.61 (acceptable) for those unfamiliar with it. Conclusion: The Intervention Setting Ontology can be used to code information from diverse sources, annotate the setting characteristics of existing intervention evaluation reports and guide future reporting