39 resultados para GST and incapacitated entities


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The quantity and quality of spatial data are increasing rapidly. This is particularly evident in the case of movement data. Devices capable of accurately recording the position of moving entities have become ubiquitous and created an abundance of movement data. Valuable knowledge concerning processes occurring in the physical world can be extracted from these large movement data sets. Geovisual analytics offers powerful techniques to achieve this. This article describes a new geovisual analytics tool specifically designed for movement data. The tool features the classic space-time cube augmented with a novel clustering approach to identify common behaviour. These techniques were used to analyse pedestrian movement in a city environment which revealed the effectiveness of the tool for identifying spatiotemporal patterns. © 2014 Taylor & Francis.

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Learning has an important position in the development of employees and their expertise. This article focuses on the role and utilization of intra and interorganizational formal and informal learning within different types of learning networks. Specifically, we investigate different types of networks (inter- or intraorganizational) and different types of learning (formal or informal) that can occur within such networks. Our qualitative case study is based on 46 expert interviews involving 49 interviewees, through which we explore how formal and informal learning was used in the development and implementation of quality improvement initiatives at a large public teaching hospital in Portugal. Our analysis suggests that formal and informal learning can take place within different types of learning networks that draw on internal resources as well as on the collaboration with external entities. The article argues that it is important for HRD managers, seeking to support organizational learning, to understand how different types of learning take place, and which features of learning networks support these processes.

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Two sets of issues in the area of law and religion have generated a large share of attention and controversy across a wide number of countries and jurisdictions in recent years. The first set of issues relates to the autonomy of churches and other religiously affiliated entities such as schools and social service organisations in their hiring and personnel decisions, involving the question of how far, if at all, such entities should be free from the influence and oversight of the state. The second set of issues involves the presence of religious symbols in the public sphere, such as in state schools or on public lands, involving the question of how far the state should be free from the influence of religion. Although these issues – freedom of religion from the state, and freedom of the state from religion – could be viewed as opposite sides of the same coin, they are almost always treated as separate lines of inquiry, and the implications of each for the other have not been the subject of much scrutiny. In this Introduction, we consider whether insights might be drawn from thinking about these issues both from a comparative law perspective and also from considering these two lines of cases together.

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During recent years, news headlines have been rife with criticisms of the risk management practices of public and private sector entities. These criticisms have often been accompanied by calls for greater transparency in the way government entities manage risks and communicate dangers to the public. Similarly, in the private sector, the internationalisation of economic activity has heightened concerns over the potential adverse implications of mismanagement and financial scandals, and has led to calls for greater regulation and supervision. While the responses of public sector agencies and private sector actors to these challenges have differed, they share a common acknowledgement that effective governance relies on the pro-active identification, assessment, and management of risks as well as appropriate regulatory frameworks.

This edited book covers a number of divergent topics illustrating the emergence of several novel themes in the area of economic and social risks. As a communality, these novel themes relate to the complexity in which human activity in this late stage of capitalist development is embedded. This risk-generating complexity, in turn, can be observed at several levels, including workplace hazards, governance problems within the private sector or the intersection between public and private, and in relation to the economic risks faced by larger entities such as national governments.

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Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member.

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Homotypic fusion between early endosomes requires the phosphatidylinositol 3-phosphate (PI3P)-binding protein, Early Endosomal Autoantigen 1 (EEA1). We have investigated the role of other proteins that interact with EEA1 in the fusion of early endosomes derived from Baby Hamster Kidney (BHK) cells. We confirm a requirement for syntaxin 13, but additionally show that the assay is equally sensitive to reagents specifically targeted against syntaxin 6. Binding of EEA1 to immobilised GST-syntaxin 6 and 13 was directly compared; only syntaxin 6 formed a stable complex with EEA1. Early endosome fusion requires the release of intravesicular calcium, and calmodulin plays a vital role in the fusion pathway, as judged by sensitivity to antagonists. We demonstrate that both EEA1 and syntaxin 13 interact with calmodulin. In the case of EEA1, binding to calmodulin requires an IQ domain, which is adjacent to a C-terminal FYVE domain that specifically binds to PI3P. We have assessed the influence of protein binding partners on EEA1 interaction with PI3P and find that both calmodulin and rab5-GTP are antagonistic to PI3P binding, whilst syntaxins 6 and 13 have no effect. These studies reveal a complex network of interactions between the proteins required for endosome fusion.

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In the 21st century, information has become the most valuable resource that is available to modern societies. Thus, great efforts have been made to develop new information processing and storage techniques. Chemistry can offer a wide variety of computing paradigms that are closely related to the natural processes found in living organisms (e.g., in the nervous systems of animals). Moreover, these phenomena cannot be reproduced easily by solely using silicon-based technology. Other great advantages of molecular-scale systems include their simplicity and the diversity of interactions that occur among them. Thus, devices constructed using chemical entities may be programmed to deal with different information carriers (photons, electrons, ions, and molecules), possibly surpassing the capabilities of classic electronic circuits.

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This paper examines the expression of ideas about love, marriage and divorce in Serglige Con Culainn. It is argued that the two versions of the tale, both of which are incomplete, exhibit distinctive approaches to love and the portrayal of the female characters. The earlier recension depicts male desire as a violent attack by Otherworld women that renders the man incapacitated. The later version provides a radically different view, offering a strikingly sympathetic portrait of the two female protagonists which may suggest a female audience. This version gives a remarkable insight into sexual mores and marital breakdown in a protracted and detailed negotiation involving the three main characters. It reveals tensions between male and female views of marriage and particularly of the practice of concubinage. It values loyalty between married partners over the fulfilment of desire and demonstrates the enduring and destructive effects of passion which are healed here only through magical interventions.

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Background: Vasodilator-Stimulated Phosphoprotein (VASP) is involved in the inhibition of agonist-induced platelet aggregation by cyclic nucleotides and the adhesion of platelets to the vascular wall. αIIbβ3 is the main integrin responsible for platelet activation and Rap1b plays a key role in integrin signalling. We investigated whether VASP is involved in the regulation of Rap1b in platelets since VASP-null platelets exhibit augmented adhesion to endothelial cells in vivo.

Methods: Washed platelets from wild type and VASP-deficient mice were stimulated with thrombin, the purinergic receptors agonist ADP, or the thromboxane A2 receptor agonist U46619 and Rap1b activation was measured using the GST-RalGDS-RBD binding assay. Interaction of VASP and Crkl was investigated by co-immunoprecipitation, confocal microscopy, and pull-down assays using Crkl domains expressed as GST-fusion proteins.

Results: Surprisingly, we found that activation of Rap1b in response to thrombin, ADP, or U46619 was significantly reduced in platelets from VASP-null mice compared to platelets from wild type mice. However, inhibition of thrombin-induced activation of Rap1b by nitric oxide was similar in platelets from wild type and VASP-null mice indicating that the NO/cGMP/PKG pathway controls inhibition of Rap1b independently from VASP. To understand how VASP regulated Rap1b, we investigated association between VASP and the Crk-like protein (Crkl), an adapter protein which activates the Rap1b guanine nucleotide exchange factor C3G. We demonstrated the formation of a Crkl/VASP complex by showing that: 1) Crkl co-immunoprecipitated VASP from platelet lysates; 2) Crkl and VASP dynamically co-localized at actin-rich protrusions reminiscent of focal adhesions, filopodia, and lamellipodia upon platelet spreading on fibronectin; 3) recombinant VASP bound directly to the N-terminal SH3 domain of Crkl; 4) PKA-mediated VASP phosphorylation on Ser157 abrogated the binding of Crkl.

Conclusions: We identified Crkl as a novel protein interacting with VASP in platelets. We propose that the C3G/Crkl/VASP complex plays a role in the regulation of Rap1b and this explains, at least in part, the reduced agonist-induced activation of Rap1b in VASP-null platelets. In addition, the fact that PKA-dependent VASP phosphorylation abrogated its interaction with Crkl may provide, at least in part, a rationale for the PKA-dependent inhibition of Rap1b and platelet aggregation.