Weak refinement in Z

An important aspect in the specification of distributed systems is the role of the internal (or unobservable) operation. Such operations are not part of the user interface (i.e. the user cannot invoke them), however, they are essential to our understanding and correct modelling of the system. Various conventions have been employed to model internal operations when specifying distributed systems in Z. If internal operations are distinguished in the specification notation, then refinement needs to deal with internal operations in appropriate ways. However, in the presence of internal operations, standard Z refinement leads to undesirable implementations. In this paper we present a generalization of Z refinement, called weak refinement, which treats internal operations differently from observable operations when refining a system. We illustrate some of the properties of weak refinement through a specification of a telecommunications protocol

Great Canadian Lagerstätten 3. Late Ordovician Konservat-Lagerstätten in Manitoba

Konservat-Lagerstätten, deposits in which soft-bodied or lightly sclerotized fossils are preserved, are very rare in Ordovician strata. Three significant sites are known from Upper Ordovician rocks in Manitoba: at Cat Head – McBeth Point, William Lake, and Airport Cove. These sites are in two distinct sedimentary basins: the former two are in the Williston Basin, while the latter is in the Hudson Bay Basin. All three sites contain marine fossils, but each has a different assemblage that contributes a distinct piece of the diversity picture. Important groups represented at one or more of the sites include seaweeds (algae), sponges, cnidarian medusae (jellyfish), conulariids, trilobites, eurypterids, xiphosurids (horseshoe crabs), and pycnogonids (‘sea spiders’). The different biotas reflect depositional conditions at each site. Many of the fossils are unknown elsewhere in the Ordovician at the family level or higher. The province of Manitoba therefore makes a significant contribution to knowledge of Late Ordovician biodiversity.SOMMAIRELes lagerstätten de conservation, ces sédiments contenant des fossiles d’organismes à corps mou ou légèrement sclérotisés particulièrement bien conservés, sont très rares dans les strates ordoviciennes.  Trois sites d’importance sont connus dans des roches de l'Ordovicien supérieur à Cat Head, Manitoba, soit McBeth Point, William Lake et  Airport Cove.  Ces sites sont situés dans deux bassins sédimentaires distincts : les deux premiers sont situés dans le bassin de Williston, tandis que le second est situé dans le bassin de la baie d'Hudson.  Les trois sites contiennent des fossiles marins, mais chacun présente un assemblage différent, chacun montrant une composante distincte de la diversité biologique d’alors.  Les groupes les plus importants représentés, dans un ou plusieurs de ces sites, sont les algues, les éponges, les cnidarian medusae (méduses), les conularides, les trilobites, les euryptérides, xiphosurides (limules) et pycnogonides.  Les différents biotopes reflètent les conditions de dépôt de chaque site.  Nombre de ces fossiles sont inconnus ailleurs dans l'Ordovicien, au niveau de la famille ou du taxon supérieur de la classification.  Ainsi, la province du Manitoba offre-t-elle une contribution importante à la connaissance de la biodiversité de l'Ordovicien supérieur

Cell Cycle Phase-Specific Surface Expression of Nerve Growth Factor Receptors TrkA and p75NTR

[EN]Expression of the nerve growth factor (NGF) receptors TrkA and p75NTR was found to vary at the surface of PC12 cells in a cell cycle phase-specific manner. This was evidenced by using flow cytometric and microscopic analysis of cell populations labeled with antibodies to the extracellular domains of both receptors. Differential expression of these receptors also was evidenced by biotinylation of surface proteins and Western analysis, using antibodies specific for the extracellular domains of TrkA and p75NTR. TrkA is expressed most strongly at the cell surface in M and early G1 phases, whereas p75NTR is expressed mainly in late G1, S, and G2 phases. This expression reflects the molecular and cellular responses to NGF in specific phases of the cell cycle; in the G1 phase NGF elicits both the anti-mitogenic effect, i.e., inhibition of the G1 to S transition, and the differentiation response whereas a survival effect is provoked elsewhere in the cell cycle. A model is proposed relating these responses to the surface expression of the two receptors. These observations open the way for novel approaches to the investigation of the mechanism of NGF signal transduction

EXACT2: the semantics of biomedical protocols

© 2014 Soldatova et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: The reliability and reproducibility of experimental procedures is a cornerstone of scientific practice. There is a pressing technological need for the better representation of biomedical protocols to enable other agents (human or machine) to better reproduce results. A framework that ensures that all information required for the replication of experimental protocols is essential to achieve reproducibility. Methods: We have developed the ontology EXACT2 (EXperimental ACTions) that is designed to capture the full semantics of biomedical protocols required for their reproducibility. To construct EXACT2 we manually inspected hundreds of published and commercial biomedical protocols from several areas of biomedicine. After establishing a clear pattern for extracting the required information we utilized text-mining tools to translate the protocols into a machine amenable format. We have verified the utility of EXACT2 through the successful processing of previously ‘unseen’ (not used for the construction of EXACT2) protocols. Results: The paper reports on a fundamentally new version EXACT2 that supports the semantically-defined representation of biomedical protocols. The ability of EXACT2 to capture the semantics of biomedical procedures was verified through a text mining use case. In this EXACT2 is used as a reference model for text mining tools to identify terms pertinent to experimental actions, and their properties, in biomedical protocols expressed in natural language. An EXACT2-based framework for the translation of biomedical protocols to a machine amenable format is proposed. Conclusions: The EXACT2 ontology is sufficient to record, in a machine processable form, the essential information about biomedical protocols. EXACT2 defines explicit semantics of experimental actions, and can be used by various computer applications. It can serve as a reference model for for the translation of biomedical protocols in natural language into a semantically-defined format.This work has been partially funded by the Brunel University BRIEF award and a grant from Occams Resources

A critical role for Kalirin in NGF signaling through TrkA

Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low concentration of NGF. Furthermore, elevated Kalirin expression resulted in catalytic activation of TrkA, as demonstrated by in vitro kinase assays and increased NGF-stimulated cellular activation of Rac, Mek, and CREB. Domain mapping demonstrated that the N-terminal Kalirin pleckstrin homology domain mediates the interaction with TrkA. The effects of Kalirin on TrkA provide a molecular basis for the requirement of Kalirin in process extension from PC12 cells and for previously observed effects on axonal extension and dendritic maintenance. The interaction of TrkA with the pleckstrin homology domain of Kalirin may be one example of a general mechanism whereby receptor/Rho GEF pairings play an important role in receptor tyrosine kinase activation and signal transduction